TW202239958A - Composition for improving joint function - Google Patents

Composition for improving joint function Download PDF

Info

Publication number
TW202239958A
TW202239958A TW111101373A TW111101373A TW202239958A TW 202239958 A TW202239958 A TW 202239958A TW 111101373 A TW111101373 A TW 111101373A TW 111101373 A TW111101373 A TW 111101373A TW 202239958 A TW202239958 A TW 202239958A
Authority
TW
Taiwan
Prior art keywords
strain
bifidobacterium
joint function
lactobacillus
lactococcus
Prior art date
Application number
TW111101373A
Other languages
Chinese (zh)
Inventor
中野礼彪
安枝武彦
瀬戸泰幸
Original Assignee
日商雪印惠乳業股份有限公司
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 日商雪印惠乳業股份有限公司 filed Critical 日商雪印惠乳業股份有限公司
Publication of TW202239958A publication Critical patent/TW202239958A/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING THEREOF
    • A23C9/00—Milk preparations; Milk powder or milk powder preparations
    • A23C9/12—Fermented milk preparations; Treatment using microorganisms or enzymes
    • A23C9/123—Fermented milk preparations; Treatment using microorganisms or enzymes using only microorganisms of the genus lactobacteriaceae; Yoghurt
    • A23C9/1234—Fermented milk preparations; Treatment using microorganisms or enzymes using only microorganisms of the genus lactobacteriaceae; Yoghurt characterised by using a Lactobacillus sp. other than Lactobacillus Bulgaricus, including Bificlobacterium sp.
    • A—HUMAN NECESSITIES
    • A21—BAKING; EDIBLE DOUGHS
    • A21D—TREATMENT, e.g. PRESERVATION, OF FLOUR OR DOUGH, e.g. BY ADDITION OF MATERIALS; BAKING; BAKERY PRODUCTS; PRESERVATION THEREOF
    • A21D13/00—Finished or partly finished bakery products
    • A21D13/40—Products characterised by the type, form or use
    • A21D13/45—Wafers
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING THEREOF
    • A23C19/00—Cheese; Cheese preparations; Making thereof
    • A23C19/02—Making cheese curd
    • A23C19/032—Making cheese curd characterised by the use of specific microorganisms, or enzymes of microbial origin
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K10/00—Animal feeding-stuffs
    • A23K10/10—Animal feeding-stuffs obtained by microbiological or biochemical processes
    • A23K10/16—Addition of microorganisms or extracts thereof, e.g. single-cell proteins, to feeding-stuff compositions
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K10/00—Animal feeding-stuffs
    • A23K10/10—Animal feeding-stuffs obtained by microbiological or biochemical processes
    • A23K10/16—Addition of microorganisms or extracts thereof, e.g. single-cell proteins, to feeding-stuff compositions
    • A23K10/18—Addition of microorganisms or extracts thereof, e.g. single-cell proteins, to feeding-stuff compositions of live microorganisms
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L21/00—Marmalades, jams, jellies or the like; Products from apiculture; Preparation or treatment thereof
    • A23L21/10—Marmalades; Jams; Jellies; Other similar fruit or vegetable compositions; Simulated fruit products
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L9/00—Puddings; Cream substitutes; Preparation or treatment thereof
    • A23L9/10—Puddings; Dry powder puddings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/745—Bifidobacteria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/20—Bacteria; Culture media therefor
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/20—Bacteria; Culture media therefor
    • C12N1/205—Bacterial isolates
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/306—Foods, ingredients or supplements having a functional effect on health having an effect on bone mass, e.g. osteoporosis prevention
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2400/00—Lactic or propionic acid bacteria
    • A23V2400/11—Lactobacillus
    • A23V2400/181—Salivarius
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2400/00—Lactic or propionic acid bacteria
    • A23V2400/21—Streptococcus, lactococcus
    • A23V2400/239—Oralis
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2400/00—Lactic or propionic acid bacteria
    • A23V2400/51—Bifidobacterium
    • A23V2400/533—Longum
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
    • C12R2001/00—Microorganisms ; Processes using microorganisms
    • C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
    • C12R2001/00—Microorganisms ; Processes using microorganisms
    • C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
    • C12R2001/225—Lactobacillus
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
    • C12R2001/00—Microorganisms ; Processes using microorganisms
    • C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
    • C12R2001/225—Lactobacillus
    • C12R2001/23—Lactobacillus acidophilus
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
    • C12R2001/00—Microorganisms ; Processes using microorganisms
    • C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
    • C12R2001/46—Streptococcus ; Enterococcus; Lactococcus

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Microbiology (AREA)
  • Engineering & Computer Science (AREA)
  • Mycology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Molecular Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Biotechnology (AREA)
  • Polymers & Plastics (AREA)
  • Food Science & Technology (AREA)
  • Epidemiology (AREA)
  • Wood Science & Technology (AREA)
  • Genetics & Genomics (AREA)
  • Biomedical Technology (AREA)
  • Biochemistry (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • General Engineering & Computer Science (AREA)
  • Virology (AREA)
  • Nutrition Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Rheumatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Immunology (AREA)
  • Physiology (AREA)
  • Animal Husbandry (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Sealing Material Composition (AREA)

Abstract

The present invention addresses the problem of providing: a composition for improving joint function, which promotes the proliferation of cartilage cells and inhibits the production of inflammation factors, cartilage matrix degradation factors, pain factors and nerve elongation factors by synovial cells, and, therefore, which is useful for preventing and treating various joint diseases such as osteoarthritis represented by osteoarthritis of the knee and rheumatoid arthritis; and products for improving joint function such as a food or beverage, a feed and a medicine each comprising the aforesaid composition. A composition for improving joint function that comprises cells of a bacterium belonging to the genus Lactobacillus, Lactococcus, Streptococcus or Bifidobacterium or a culture thereof. An agent for improving joint function, a food or beverage for improving joint function, a nutritional composition for improving joint function, a feed for improving joint function or a medicine for improving joint function, each being characterized by comprising the aforesaid composition for improving joint function.

Description

關節功能改善用組成物Composition for improving joint function

本發明係關於可改善關節功能之關節功能改善用組成物。本發明係有促進軟骨細胞之增殖的作用，此外，有抑制滑膜細胞所致之發炎因子、軟骨基質分解因子、疼痛因子、神經伸長因子之產生的作用。藉由本發明，可提供對於以退化性膝關節炎為代表之退化性關節炎或類風濕性關節炎等各種關節疾病之預防或治療有效用之具有關節功能改善作用的素材。另外，本發明係關於含有該具有關節功能改善作用之素材的關節功能改善劑、關節功能改善用飲食品、關節功能改善用營養組成物、關節功能改善用飼料或關節功能改善用醫藥品。The present invention relates to a composition for improving joint function which can improve joint function. The present invention has the effect of promoting the proliferation of chondrocytes, and in addition, has the effect of inhibiting the production of inflammatory factors, cartilage matrix decomposition factors, pain factors and nerve elongation factors caused by synoviocytes. According to the present invention, it is possible to provide a material having a joint function-improving effect that is effective for the prevention or treatment of various joint diseases such as osteoarthritis represented by osteoarthritis or rheumatoid arthritis. In addition, the present invention relates to a joint function improving agent, a joint function improving food and drink, a joint function improving nutritional composition, a joint function improving feed, or a joint function improving drug containing the material having the joint function improving effect.

近年來，日本人的平均壽命係超過80歲，迎來約4人中有1人為65歲以上的超高齡社會。伴隨該點，運動器官障礙的罹患率也不斷地增加。於2007年，日本整形外科學會為了推進關於運動器官之健康維持、增進、照護之國民以及醫師的意識改革，而提倡「運動障礙症候群(運動器官症候群，Locomotive Syndrome)」的新單詞。運動障礙症候群係表示運動器官的功能障礙導致為需要照護之狀態及需要照護之風險高的狀態，運動器官係總括包含骨頭、關節、韌帶、脊椎、脊髓、肌肉、肌腱、末梢神經等，具有支撐身體、進行動作之功能的器官。就於此等運動器官可見之具代表性的疾病及功能障礙而言，可列舉骨質疏鬆症或肌肉減少症、退化性關節炎等。In recent years, the average life expectancy of Japanese people has exceeded 80 years, and about 1 out of 4 people is over 65 years old. Along with this, the attack rate of locomotor disorders is also increasing. In 2007, the Japanese Society of Plastic Surgery advocated the new word "Locomotive Syndrome" in order to promote the awareness reform of citizens and physicians about the maintenance, improvement and care of locomotor organs. Dyskinesia Syndrome refers to a condition requiring care and a high risk of needing care due to dysfunction of motor organs. The motor system includes bones, joints, ligaments, spine, spinal cord, muscles, tendons, peripheral nerves, etc., and supports the body. , The organ that carries out the function of action. Osteoporosis, sarcopenia, osteoarthritis, and the like are exemplified as typical diseases and dysfunctions seen in these motor organs.

於日本，退化性膝關節炎之病患數目於2009年推測為約2530萬人，50歲以上有2~3成罹患該疾病，係病患數目最多的關節疾病。作為退化性關節炎發病的原因，據認為有年齡增長及遺傳之因素導致之關節構成要素之變性、或者肥胖、勞動、運動導致對於關節之負荷等。伴隨著退化性關節炎的發病，於圍繞關節周圍之滑膜組織併發發炎，而加速包括軟骨之減少、消失之關節的變形。此外，伴隨著發炎之併發及關節的變形，大部分的退化性關節炎患者會感受疼痛、QOL(生活品質，Quality of life)明顯地下降。 關節軟骨中係沒有血管或神經細胞，故若一旦受到損傷則難以自然地復原。因此，在退化性關節炎之症狀為輕度的情況，會採用溫熱療法或牽引等物理療法、或者使用止痛藥或抗發炎藥的緩和療法。然而，現存之類固醇或非類固醇系之抗發炎劑，有著如腎上腺功能障礙或小腸障礙的副作用大的問題。此外，在重度症狀的情況，會實施對於關節注入玻尿酸或藉由手術置換為人工關節。然而，為了從日常生活來減輕退化性關節炎之症狀並改善患者之QOL，於該疾病之性質上，有著藉由在日常安全且長期間地攝取食品或含於食品之有效成分，來維持患者自身之軟骨之形狀、預防或修復變形、或者使消失之軟骨再生、或者抑制關節周圍之發炎及疼痛的需求。 In Japan, the number of patients with degenerative knee arthritis was estimated to be about 25.3 million in 2009, and 20% to 30% of people over the age of 50 suffer from this disease, which is the joint disease with the largest number of patients. The cause of the onset of osteoarthritis is considered to be the degeneration of joint constituent elements due to aging and genetic factors, or the load on joints due to obesity, labor, and exercise. With the onset of osteoarthritis, the synovial tissue surrounding the joint becomes inflamed, which accelerates joint deformation including cartilage loss and disappearance. In addition, with the concurrent inflammation and joint deformation, most patients with osteoarthritis will feel pain and QOL (Quality of life, Quality of life) will decline significantly. There are no blood vessels or nerve cells in articular cartilage, so once damaged, it is difficult to recover naturally. Therefore, when the symptoms of osteoarthritis are mild, physical therapy such as thermotherapy or traction, or palliative therapy using painkillers or anti-inflammatory drugs is used. However, the existing steroidal and non-steroidal anti-inflammatory agents have the problem of large side effects such as adrenal dysfunction and intestinal disturbance. In addition, in the case of severe symptoms, injection of hyaluronic acid into the joint or replacement of the joint with an artificial joint will be performed. However, in order to alleviate the symptoms of osteoarthritis and improve the patient's QOL from daily life, in view of the nature of the disease, there is a need to maintain the patient's life by taking food or active ingredients contained in food safely and for a long period of time in daily life. Shape of own cartilage, prevent or repair deformation, or regenerate lost cartilage, or suppress inflammation and pain around joints.

到目前為止，有揭示以含有枸杞萃取物為特徵之關節功能改善劑(專利文獻1)。然而，至今尚未知曉藉由乳酸菌或雙歧桿菌之菌體成分或其培養物對於軟骨細胞或滑膜細胞直接作用，會促進軟骨細胞之增殖、抑制滑膜細胞所致之發炎因子、軟骨基質分解因子、疼痛因子、神經伸長因子的產生。 [先前技術文獻] [專利文獻] So far, a joint function improving agent characterized by containing wolfberry extract has been disclosed (Patent Document 1). However, it is not yet known that the bacterial components of lactic acid bacteria or bifidobacteria or their cultures directly act on chondrocytes or synoviocytes to promote the proliferation of chondrocytes, inhibit inflammatory factors caused by synoviocytes, and decompose cartilage matrix Factors, pain factors, nerve elongation factor production. [Prior Art Literature] [Patent Document]

[專利文獻1]日本特開第2020-94015號公報[Patent Document 1] Japanese Patent Laid-Open No. 2020-94015

[發明所欲解決之課題][Problem to be Solved by the Invention]

本發明之課題係提供能於日常安全且長期間攝取、有促進軟骨細胞之增殖的作用、修正或再生已變形或消失之軟骨、緩和疼痛之效果優良、具有關節功能改善作用的素材。此外，本發明之課題係提供具有抑制滑膜細胞所致之發炎因子、軟骨基質分解因子、疼痛因子、神經伸長因子之產生的作用的素材。該素材係對於以退化性膝關節炎為代表之退化性關節炎或類風濕性關節炎等各種關節疾病之預防或治療有效用。此外，本發明之課題係提供摻合了具有關節功能改善作用之素材的關節功能改善劑、關節功能改善用飲食品、關節功能改善用營養組成物、關節功能改善用飼料或關節功能改善用醫藥品。上述素材有著促進軟骨細胞之增殖的作用。此外，上述素材係有抑制滑膜細胞所致之發炎因子、軟骨基質分解因子、疼痛因子、神經伸長因子之產生的作用，故修正或再生已變形或消失之軟骨、緩和疼痛之效果優良。 [解決課題之手段] The object of the present invention is to provide a material that can be taken safely and for a long time in daily life, has the effect of promoting the proliferation of chondrocytes, corrects or regenerates deformed or lost cartilage, has an excellent effect of relieving pain, and has the effect of improving joint function. In addition, the object of the present invention is to provide a material having an effect of inhibiting the production of synoviocyte-induced inflammatory factors, cartilage matrix decomposition factors, pain factors, and nerve elongation factors. The material is effective in the prevention or treatment of various joint diseases such as degenerative arthritis represented by degenerative knee arthritis or rheumatoid arthritis. In addition, the object of the present invention is to provide a joint function improving agent, a food and drink for joint function improvement, a nutritional composition for joint function improvement, a feed for joint function improvement, or a medicine for joint function improvement, which incorporate materials having a joint function improving effect. Taste. The above materials have the effect of promoting the proliferation of chondrocytes. In addition, the above-mentioned materials have the effect of inhibiting the production of inflammatory factors, cartilage matrix decomposition factors, pain factors, and nerve elongation factors caused by synoviocytes, so they have excellent effects in repairing or regenerating deformed or lost cartilage and alleviating pain. [Means to solve the problem]

本案發明者們，為了解決上述課題深入研究之結果，發現數種乳酸菌或雙歧桿菌有促進軟骨細胞之增殖的作用，或有抑制滑膜細胞所致之發炎因子、軟骨基質分解因子、疼痛因子、神經伸長因子之產生的作用，而完成了本發明。The inventors of this case, in order to solve the above problems, found that several lactic acid bacteria or bifidobacteria can promote the proliferation of chondrocytes, or inhibit the inflammatory factors, cartilage matrix decomposition factors, and pain factors caused by synoviocytes. , The role of the production of nerve elongation factor, and completed the present invention.

亦即，本發明係以下構成而成者。 (1)一種關節功能改善用組成物，含有屬於乳桿菌(Lactobacillus)屬、乳球菌(Lactococcus)屬、鏈球菌(Streptococcus)屬、或雙歧桿菌(Bifidobacterium)屬的菌的菌體及/或其培養物作為有效成分。 (2)如(1)之關節功能改善用組成物，其中，屬於乳桿菌屬、乳球菌屬、鏈球菌屬、或雙歧桿菌屬的菌，係選自嗜酸乳桿菌(Lactobacillus acidophilus)、瑞士乳桿菌(Lactobacillus helveticus)、唾液乳桿菌(Lactobacillus salivarius)、乳酸乳球菌(Lactococcus lactis)、勞氏乳球菌(Lactococcus laudensis)、口腔鏈球菌(Streptococcus oralis)、長雙歧桿菌(Bifidobacterium longum)、假長雙歧桿菌(Bifidobacterium pseudolongum)、嗜熱雙歧桿菌(Bifidobacterium thermophilum)中之一種以上。 (3)如(2)之關節功能改善用組成物，其中，屬於唾液乳桿菌、乳酸乳球菌、或長雙歧桿菌的菌，係屬於唾液乳桿菌唾液亞種 (Lactobacillus salivarius subsp. salivarius)、乳酸乳球菌乳酸亞種 (Lactococcus lactis subsp. lactis)、乳酸乳球菌乳脂亞種 (Lactococcus lactis subsp. cremoris)、或長雙歧桿菌嬰兒亞種 (Bifidobacterium longum subsp. infantis)的菌。 (4)如(1)至(3)中任一項之關節功能改善用組成物，其中，屬於乳桿菌屬、乳球菌屬、鏈球菌屬、或雙歧桿菌屬的菌，係選自嗜酸乳桿菌(Lactobacillus acidophilus)SBT2062菌株(FERM BP-11075)、瑞士乳桿菌(Lactobacillus helveticus)SBT2161菌株(NITE BP-1707)、SBT2171菌株(FERM BP-5445)、唾液乳桿菌(Lactobacillus salivarius)SBT2687菌株(NITE ABP-03331)、SBT2651菌株(NITE P-03330)、唾液乳桿菌唾液亞種(Lactobacillus salivarius subsp. salivarius)SBT2670菌株(FERM P-13247)、乳酸乳球菌乳酸亞種(Lactococcus lactis subsp. lactis)SBT0625菌株(NITE P-03078)、乳酸乳球菌乳脂亞種(Lactococcus lactis subsp. cremoris)SBT11373菌株(NITE P-03246)、勞氏乳球菌(Lactococcus laudensis)SBT11178菌株(NITE P-03333)、口腔鏈球菌(Streptococcus oralis)SBT0320菌株(NITE P-03332)、長雙歧桿菌(Bifidobacterium longum)SBT2928菌株(FERM P-10657)、長雙歧桿菌嬰兒亞種(Bifidobacterium longum subsp. infantis)SBT2785菌株(NITE P-03328)、假長雙歧桿菌(Bifidobacterium pseudolongum)SBT2922菌株(NITE P-02984)、嗜熱雙歧桿菌(Bifidobacterium thermophilum)SBT2992菌株(NITE P-03364)中之一種以上。 (5)一種關節功能改善劑、關節功能改善用飲食品、關節功能改善用營養組成物、關節功能改善用飼料或關節功能改善用醫藥品，其特徵在於，含有如(1)至(4)中任一項之關節功能改善用組成物。 (6)一種新穎之乳酸菌，係唾液乳桿菌(Lactobacillus salivarius)SBT2687菌株。 (7)一種新穎之乳酸菌，係唾液乳桿菌(Lactobacillus salivarius)SBT2651菌株。 (8)一種新穎之乳酸菌，係勞氏乳球菌(Lactococcus laudensis)SBT11178菌株。 (9)一種新穎之乳酸菌，係口腔鏈球菌(Streptococcus oralis) SBT0320菌株。 (10)一種新穎之雙歧桿菌，係長雙歧桿菌嬰兒亞種(Bifidobacterium longum subsp. infantis)SBT2785菌株。 (11)一種新穎之雙歧桿菌，係嗜熱雙歧桿菌(Bifidobacterium thermophilum)SBT2992菌株。 (12)一種屬於乳桿菌(Lactobacillus)屬、乳球菌(Lactococcus)屬、鏈球菌(Streptococcus)屬、或雙歧桿菌(Bifidobacterium)屬的菌的菌體及/或其培養物的用途，係用來製造關節功能改善用組成物。 (13)一種屬於乳桿菌(Lactobacillus)屬、乳球菌(Lactococcus)屬、鏈球菌(Streptococcus)屬、或雙歧桿菌(Bifidobacterium)屬的菌的菌體及/或其培養物，係用來改善關節功能。 (14)一種關節功能改善方法，包含下述步驟： 將有效量之屬於乳桿菌(Lactobacillus)屬、乳球菌(Lactococcus)屬、鏈球菌(Streptococcus)屬、或雙歧桿菌(Bifidobacterium)屬的菌的菌體及/或其培養物，給需要的對象攝取、或投予給需要的對象。 (15)一種促進軟骨細胞增殖用、抑制發炎因子產生用、抑制軟骨基質分解因子產生用、抑制疼痛因子產生用、及/或抑制神經伸長因子產生用組成物，含有屬於乳桿菌(Lactobacillus)屬、乳球菌(Lactococcus)屬、鏈球菌(Streptococcus)屬、或雙歧桿菌(Bifidobacterium)屬之菌的菌體及/或其培養物作為有效成分。 [發明之效果] That is, the present invention is constituted as follows. (1) A composition for improving joint function, comprising cells of bacteria belonging to the genus Lactobacillus, Lactococcus, Streptococcus, or Bifidobacterium and/or Its culture is used as an active ingredient. (2) The composition for improving joint function according to (1), wherein the bacteria belonging to the genus Lactobacillus, Lactococcus, Streptococcus, or Bifidobacterium are selected from the group consisting of Lactobacillus acidophilus, Lactobacillus helveticus, Lactobacillus salivarius, Lactococcus lactis, Lactococcus laudensis, Streptococcus oralis, Bifidobacterium longum, One or more of Bifidobacterium pseudolongum and Bifidobacterium thermophilum. (3) The composition for improving joint function as in (2), wherein the bacteria belonging to Lactobacillus salivarius, Lactococcus lactis, or Bifidobacterium longum belong to Lactobacillus salivarius subsp. salivarius, Lactococcus lactis subsp. lactis, Lactococcus lactis subsp. cremoris, or Bifidobacterium longum subsp. infantis. (4) The composition for improving joint function according to any one of (1) to (3), wherein the bacteria belonging to the genus Lactobacillus, Lactococcus, Streptococcus, or Bifidobacterium are selected from the group consisting of Lactobacillus acidophilus SBT2062 strain (FERM BP-11075), Lactobacillus helveticus SBT2161 strain (NITE BP-1707), SBT2171 strain (FERM BP-5445), Lactobacillus salivarius SBT2687 strain (NITE ABP-03331), SBT2651 strain (NITE P-03330), Lactobacillus salivarius subsp. salivarius SBT2670 strain (FERM P-13247), Lactococcus lactis subsp. lactis ) SBT0625 strain (NITE P-03078), Lactococcus lactis subsp. cremoris SBT11373 strain (NITE P-03246), Lactococcus laudensis SBT11178 strain (NITE P-03333), oral Streptococcus oralis SBT0320 strain (NITE P-03332), Bifidobacterium longum SBT2928 strain (FERM P-10657), Bifidobacterium longum subsp. infantis SBT2785 strain (NITE P-03328), Bifidobacterium pseudolongum SBT2922 strain (NITE P-02984), Bifidobacterium thermophilum SBT2992 strain (NITE P-03364). (5) A joint function-improving agent, a joint function-improving food and drink, a joint function-improving nutrient composition, a joint function-improving feed, or a joint function-improving drug, characterized by comprising (1) to (4) A composition for improving joint function according to any one of the above. (6) A novel lactic acid bacterium, which is Lactobacillus salivarius SBT2687 strain. (7) A novel lactic acid bacterium, which is Lactobacillus salivarius SBT2651 strain. (8) A novel lactic acid bacterium, which is Lactococcus laudensis SBT11178 strain. (9) A novel lactic acid bacterium, which is Streptococcus oralis SBT0320 strain. (10) A novel bifidobacterium, which is Bifidobacterium longum subsp. infantis SBT2785 strain. (11) A novel bifidobacterium, which is Bifidobacterium thermophilum SBT2992 strain. (12) A use of bacteria and/or cultures thereof belonging to the genus Lactobacillus, Lactococcus, Streptococcus, or Bifidobacterium, for To manufacture a composition for improving joint function. (13) A bacterial cell and/or culture thereof belonging to the genus Lactobacillus, Lactococcus, Streptococcus, or Bifidobacterium, used to improve joint function. (14) A method for improving joint function, comprising the following steps: An effective amount of bacterial cells and/or cultures thereof belonging to the genus Lactobacillus, Lactococcus, Streptococcus, or Bifidobacterium is administered to the subject in need Ingest or administer to a subject in need. (15) A composition for promoting the proliferation of chondrocytes, inhibiting the production of inflammatory factors, inhibiting the production of cartilage matrix decomposition factors, inhibiting the production of pain factors, and/or inhibiting the production of nerve elongation factors, containing a composition belonging to the genus Lactobacillus , Lactococcus (Lactococcus) genus, Streptococcus (Streptococcus) genus, or Bifidobacterium (Bifidobacterium) bacterium and/or its culture as an active ingredient. [Effect of Invention]

本發明之關節功能改善用組成物係安全性高，且藉由促進軟骨細胞之增殖的作用、或者抑制滑膜細胞所致之發炎因子、軟骨基質分解因子、疼痛因子、神經伸長因子之產生的作用而得的關節功能改善作用明顯。該關節功能改善用組成物對於以退化性膝關節炎為代表之退化性關節炎或類風濕性關節炎等各種關節疾病之預防或治療有效用。此外，本發明可提高關節的功能。本發明係有促進軟骨細胞之增殖的作用，此外，有抑制滑膜細胞所致之發炎因子、軟骨基質分解因子、疼痛因子、神經伸長因子之產生的作用。因此，本發明係提供摻合了對於以退化性膝關節炎為代表之退化性關節炎或類風濕性關節炎等各種關節疾病的預防或治療有效用的關節功能改善用組成物的關節功能改善劑、關節功能改善用飲食品、關節功能改善用營養組成物、關節功能改善用飼料或關節功能改善用醫藥品。The composition for improving joint function of the present invention is highly safe, and has the effect of promoting the proliferation of chondrocytes, or inhibiting the production of inflammatory factors, cartilage matrix decomposition factors, pain factors, and nerve elongation factors caused by synoviocytes. The effect of improving joint function is obvious. The composition for improving joint function is effective for preventing or treating various joint diseases such as osteoarthritis typified by osteoarthritis of the knee or rheumatoid arthritis. In addition, the present invention can improve the function of joints. The present invention has the effect of promoting the proliferation of chondrocytes, and in addition, has the effect of inhibiting the production of inflammatory factors, cartilage matrix decomposition factors, pain factors and nerve elongation factors caused by synoviocytes. Therefore, the present invention provides a joint function improvement that incorporates a composition for improving joint function effective in the prevention or treatment of various joint diseases such as osteoarthritis typified by osteoarthritis of the knee or rheumatoid arthritis. Drugs, food and beverages for improving joint function, nutritional compositions for improving joint function, feed for improving joint function, or pharmaceuticals for improving joint function.

就本發明中能使用之乳酸菌而言，只要是具有關節功能改善作用之屬於乳桿菌(Lactobacillus)屬、乳球菌(Lactococcus)屬、鏈球菌(Streptococcus)屬的乳酸菌則使用任意者皆可，就雙歧桿菌而言，只要是具有關節功能改善作用之屬於雙歧桿菌(Bifidobacterium)屬的雙歧桿菌則使用任意者皆可。 就屬於乳桿菌屬之乳酸菌而言，可例示屬於嗜酸乳桿菌(Lactobacillus acidophilus)、瑞士乳桿菌(Lactobacillus helveticus)、唾液乳桿菌(Lactobacillus salivarius)等的乳酸菌。就屬於乳球菌屬的乳酸菌而言，可例示屬於乳酸乳球菌(Lactococcus lactis)、勞氏乳球菌(Lactococcus laudensis)等的乳酸菌。就屬於鏈球菌屬的乳酸菌而言，可例示屬於口腔鏈球菌(Streptococcus oralis)等的乳酸菌。就屬於雙歧桿菌屬的雙歧桿菌而言，可例示屬於長雙歧桿菌(Bifidobacterium longum)、假長雙歧桿菌(Bifidobacterium pseudolongum)、嗜熱雙歧桿菌(Bifidobacterium thermophilum)等的雙歧桿菌。就屬於唾液乳桿菌的乳酸菌而言，可例示唾液乳桿菌唾液亞種(Lactobacillus salivarius subsp. salivarius)等的乳酸菌。就屬於乳酸乳球菌的乳酸菌而言，可例示乳酸乳球菌乳酸亞種(Lactococcus lactis subsp. lactis)、乳酸乳球菌乳脂亞種(Lactococcus lactis subsp. cremoris)等的乳酸菌。就屬於長雙歧桿菌的雙歧桿菌而言，可例示長雙歧桿菌嬰兒亞種(Bifidobacterium longum subsp. infantis)等的雙歧桿菌。不管是乳酸菌或雙歧桿菌，皆不僅限定於例示者。 As for the lactic acid bacteria that can be used in the present invention, any lactic acid bacteria belonging to the genus Lactobacillus, Lactococcus, and Streptococcus can be used as long as they have joint function improving effects. Any bifidobacterium may be used as long as it belongs to the genus Bifidobacterium and has a joint function improving effect. Examples of lactic acid bacteria belonging to the genus Lactobacillus include lactic acid bacteria belonging to Lactobacillus acidophilus, Lactobacillus helveticus, and Lactobacillus salivarius. Examples of the lactic acid bacteria belonging to the genus Lactococcus include lactic acid bacteria belonging to Lactococcus lactis, Lactococcus laudensis, and the like. Lactic acid bacteria belonging to the genus Streptococcus include lactic acid bacteria belonging to Streptococcus oralis and the like. Examples of bifidobacteria belonging to the genus Bifidobacterium include bifidobacteria belonging to Bifidobacterium longum, Bifidobacterium pseudolongum, Bifidobacterium thermophilum and the like. Examples of lactic acid bacteria belonging to Lactobacillus salivarius include Lactobacillus salivarius subsp. salivarius and the like. Examples of lactic acid bacteria belonging to Lactococcus lactis include Lactococcus lactis subsp. lactis and Lactococcus lactis subsp. cremoris. Bifidobacteria belonging to Bifidobacterium longum include Bifidobacterium longum subsp. infantis and the like. Neither lactic acid bacteria nor bifidobacteria are limited to the examples.

本發明中可使用之嗜酸乳桿菌、瑞士乳桿菌、唾液乳桿菌、唾液乳桿菌唾液亞種、乳酸乳球菌乳酸亞種、乳酸乳球菌乳脂亞種、勞氏乳球菌、口腔鏈球菌、長雙歧桿菌、長雙歧桿菌嬰兒亞種、假長雙歧桿菌、嗜熱雙歧桿菌，可藉由16S核糖體RNA基因序列分析等一般的分類方法進行分類。 本發明尤其宜使用嗜酸乳桿菌(Lactobacillus acidophilus)SBT2062菌株(FERM BP-11075)、瑞士乳桿菌(Lactobacillus helveticus)SBT2161菌株(NITE BP-1707)、SBT2171菌株(FERM BP-5445)、唾液乳桿菌(Lactobacillus salivarius)SBT2687菌株(NITE ABP-03331)、SBT2651菌株(NITE P-03330)、唾液乳桿菌唾液亞種(Lactobacillus salivarius subsp. salivarius)SBT2670菌株(FERM P-13247)、乳酸乳球菌乳酸亞種(Lactococcus lactis subsp. lactis)SBT0625菌株(NITE P-03078)、乳酸乳球菌乳脂亞種(Lactococcus lactis subsp. cremoris)SBT11373菌株(NITE P-03246)、勞氏乳球菌(Lactococcus laudensis)SBT11178菌株(NITE P-03333)、口腔鏈球菌(Streptococcus oralis)SBT0320菌株(NITE P-03332)、長雙歧桿菌(Bifidobacterium longum)SBT2928菌株(FERM P-10657)、長雙歧桿菌嬰兒亞種(Bifidobacterium longum subsp. infantis)SBT2785菌株(NITE P-03328)、假長雙歧桿菌(Bifidobacterium pseudolongum)SBT2922菌株(NITE P-02984)、嗜熱雙歧桿菌(Bifidobacterium thermophilum)SBT2992菌株(NITE P-03364)，但不限定為此等。 Lactobacillus acidophilus, Lactobacillus helveticus, Lactobacillus salivarius, Lactobacillus salivarius subsp. salivarius, Lactococcus lactis subsp. lactis, Lactococcus lactis subsp. cremoris, Lactococcus lousei, Streptococcus oralis, Bifidobacterium, Bifidobacterium longum subsp. infantis, Bifidobacterium pseudolongum, and Bifidobacterium thermophila can be classified by general classification methods such as 16S ribosomal RNA gene sequence analysis. The present invention is especially suitable to use Lactobacillus acidophilus (Lactobacillus acidophilus) SBT2062 strain (FERM BP-11075), Lactobacillus helveticus (Lactobacillus helveticus) SBT2161 strain (NITE BP-1707), SBT2171 strain (FERM BP-5445), Lactobacillus salivarius (Lactobacillus salivarius) SBT2687 strain (NITE ABP-03331), SBT2651 strain (NITE P-03330), Lactobacillus salivarius subsp. salivarius SBT2670 strain (FERM P-13247), Lactococcus lactis subsp. (Lactococcus lactis subsp. lactis) SBT0625 strain (NITE P-03078), Lactococcus lactis subsp. cremoris SBT11373 strain (NITE P-03246), Lactococcus laudensis SBT11178 strain (NITE P-03333), Streptococcus oralis SBT0320 strain (NITE P-03332), Bifidobacterium longum SBT2928 strain (FERM P-10657), Bifidobacterium longum subsp. infantis) SBT2785 strain (NITE P-03328), Bifidobacterium pseudolongum SBT2922 strain (NITE P-02984), Bifidobacterium thermophilum SBT2992 strain (NITE P-03364), but not limited Wait for that.

本發明之關節功能改善用組成物可含有屬於乳桿菌(Lactobacillus)屬、乳球菌(Lactococcus)屬、鏈球菌(Streptococcus)屬、或雙歧桿菌(Bifidobacterium)屬的菌的菌體、及其培養物中的1種以上。本發明之有效成分亦可為來自屬於乳桿菌(Lactobacillus)屬、乳球菌(Lactococcus)屬、鏈球菌(Streptococcus)屬、或雙歧桿菌(Bifidobacterium)屬的菌的各個的菌體而得者。本發明之有效成分亦可為來自屬於乳桿菌(Lactobacillus)屬、乳球菌(Lactococcus)屬、鏈球菌(Streptococcus)屬、或雙歧桿菌(Bifidobacterium)屬的菌的各個的培養物而得者。The composition for improving joint function of the present invention may contain bacteria belonging to the genus Lactobacillus, Lactococcus, Streptococcus, or Bifidobacterium, and culture thereof 1 or more of the species. The active ingredient of the present invention may be obtained from each of bacteria belonging to the genus Lactobacillus, Lactococcus, Streptococcus, or Bifidobacterium. The active ingredient of the present invention may also be obtained from cultures of bacteria belonging to the genus Lactobacillus, Lactococcus, Streptococcus, or Bifidobacterium.

(乳酸菌或雙歧桿菌之培養法) 本發明中使用之乳酸菌或雙歧桿菌係可依循培養乳酸菌或雙歧桿菌之通常方法來進行培養。培養基可使用乳培養基或含有乳成分之培養基、不包含此之半合成培養基等各種培養基。就如此之培養基而言，可例示還原脫脂乳培養基等。能將從獲得之培養物藉由離心分離等集菌手段所分離而得之菌體直接用來作為本發明之有效成分。亦可使用經濃縮、乾燥、冷凍乾燥等的菌體，也可藉由加熱乾燥等製成死菌體。 (Cultivation method of lactic acid bacteria or bifidobacteria) The lactic acid bacteria or bifidobacteria used in the present invention can be cultivated according to the usual methods for culturing lactic acid bacteria or bifidobacteria. Various media, such as a milk medium, a medium containing a milk component, and a semi-synthetic medium not containing these, can be used as the medium. Such a medium may, for example, be a reduced skim milk medium or the like. The bacteria isolated from the obtained culture by means of collecting bacteria such as centrifugation can be directly used as the active ingredient of the present invention. Concentrated, dried, freeze-dried, etc. bacterial cells may also be used, and dead bacterial cells may also be prepared by heat-drying or the like.

不僅可使用經分離之純粹菌體，亦可使用培養物、懸浮物、其他的菌體含有物、或將菌體使用酵素或物理性的手段處理而得之細胞質或細胞壁成分。就培養物等之形態而言，不僅能例示使用了為合成培養基之MRS培養基(DIFCO公司製)、M17培養基(DIFCO公司製)、含1%葡萄糖之GAM培養基(日水製藥公司製)、還原脫脂乳培養基等一般於乳酸菌之培養中使用之培養基而得的培養物，亦能例示起司、發酵乳、乳酸菌飲料等乳製品等，並沒有特別的限定。另外，亦可使用藉由從獲得之培養物使用離心分離、過濾操作等方法，除去乳蛋白質沉澱或菌體成分所調製而得的培養上清液等。因為為固體成分少的上清液，故對於飲食品等的適用範圍廣。例如，藉由將還原脫脂乳培養物進行5,000rpm、10分鐘的離心分離，可調製培養上清液。Not only isolated pure bacteria can be used, but also cultures, suspensions, other bacteria containing substances, or cytoplasm or cell wall components obtained by treating bacteria with enzymes or physical means. In terms of the form of the culture, not only MRS medium (manufactured by DIFCO), M17 medium (manufactured by DIFCO), GAM medium (manufactured by Nissui Pharmaceutical Co., Ltd.) containing 1% glucose, and reduced Cultures obtained from culture media generally used for culturing lactic acid bacteria, such as skim milk culture medium, can also be exemplified and are not particularly limited, such as dairy products such as cheese, fermented milk, and lactic acid bacteria drinks. In addition, a culture supernatant prepared by removing milk protein precipitates or bacterial cell components from the obtained culture by centrifugation, filtration, or the like can also be used. Since it is a supernatant with little solid content, it can be widely applied to food and beverages and the like. For example, the culture supernatant can be prepared by centrifuging the reduced skim milk culture at 5,000 rpm for 10 minutes.

(新穎之乳酸菌株或新穎之雙歧桿菌株) 本發明係關於新穎之乳酸菌株或新穎之雙歧桿菌株。此等新穎之乳酸菌株或新穎之雙歧桿菌株，係唾液乳桿菌 SBT2687菌株(NITE ABP-03331)、唾液乳桿菌 SBT2651菌株(NITE P-03330)、勞氏乳球菌 SBT11178菌株(NITE P-03333)、口腔鏈球菌 SBT0320菌株(NITE P-03332)、長雙歧桿菌嬰兒亞種 SBT2785菌株(NITE P-03328)、嗜熱雙歧桿菌 SBT2992菌株(NITE P-03364)。以下，有時將同樣之乳酸菌株或雙歧桿菌株記載為「本發明之乳酸菌或雙歧桿菌」、「本發明之乳酸菌株或雙歧桿菌株」、或簡單記載為SBT2687菌株、SBT2651菌株、SBT11178菌株、SBT0320菌株、SBT2785菌株、SBT2992菌株。 此等之乳酸菌株係於2020年12月1日或2021年1月19日，寄存至獨立行政法人 製品評價技術基盤機構專利微生物寄存中心(郵遞區號292-0818 千葉縣木更津市上總鎌足2-5-8 122號室)，SBT2687菌株係以NITE ABP-03331之委託號碼寄存、SBT2651菌株係以NITE P-03330之委託號碼寄存、SBT11178菌株係以NITE P-03333之委託號碼寄存、SBT0320菌株係以NITE P-03332之委託號碼寄存、SBT2785菌株係以NITE P-03328之委託號碼寄存、SBT2992菌株係以NITE P-03364之委託號碼寄存。 本發明之乳酸菌或雙歧桿菌並不限定為上述寄存乳酸菌株或雙歧桿菌株，亦可為與此等寄存乳酸菌株或雙歧桿菌株實質上同等的乳酸菌株或雙歧桿菌株。實質上同等的乳酸菌株或雙歧桿菌株係屬於嗜酸乳桿菌、瑞士乳桿菌、唾液乳桿菌、唾液乳桿菌唾液亞種、乳酸乳球菌乳酸亞種、乳酸乳球菌乳脂亞種、勞氏乳球菌、口腔鏈球菌、長雙歧桿菌、長雙歧桿菌嬰兒亞種、假長雙歧桿菌、嗜熱雙歧桿菌之乳酸菌株或雙歧桿菌株，並具有與寄存乳酸菌株或雙歧桿菌株同樣高程度之關節功能改善作用的乳酸菌株或雙歧桿菌株。「具有與寄存乳酸菌株或雙歧桿菌株同樣高程度之關節功能改善作用的乳酸菌株或雙歧桿菌株」係指，例如藉由以下步驟1)~3)所測定之促進軟骨細胞增殖效果、或藉由步驟4)~7)所測定之抑制滑膜細胞所致之發炎因子、軟骨基質分解因子、疼痛因子、神經伸長因子之產生的效果，與各個寄存之乳酸菌株或雙歧桿菌株的促進軟骨細胞增殖效果或抑制滑膜細胞所致之發炎因子、軟骨基質分解因子、疼痛因子、神經伸長因子之產生的效果無顯著差異的乳酸菌株或雙歧桿菌株。 (Novel lactic acid bacteria strain or novel bifidobacteria strain) The present invention relates to novel lactic acid bacteria strains or novel bifidobacterium strains. These novel lactic acid bacteria strains or novel bifidobacterium strains are Lactobacillus salivarius SBT2687 strain (NITE ABP-03331), Lactobacillus salivarius SBT2651 strain (NITE P-03330), Lactococcus lousei SBT11178 strain (NITE P-03333 ), Streptococcus oralis SBT0320 strain (NITE P-03332), Bifidobacterium longum subsp. Hereinafter, the same lactic acid bacteria strain or bifidobacterium strain may be described as "lactic acid bacteria or bifidobacterium strain of the present invention", "lactic acid bacteria strain or bifidobacterium strain of the present invention", or simply described as SBT2687 strain, SBT2651 strain, SBT11178 strain, SBT0320 strain, SBT2785 strain, SBT2992 strain. These lactic acid bacteria strains were deposited on December 1, 2020 or January 19, 2021 at the Patent Microorganism Depository Center of the Independent Administrative Legal Person Product Evaluation Technology Base Organization (Zip Code 292-0818 Kamiso Kasarazu, Kisarazu City, Chiba Prefecture 2 -5-8 Room 122), the SBT2687 strain is deposited under the entrustment number of NITE ABP-03331, the SBT2651 strain is deposited under the entrustment number of NITE P-03330, the SBT11178 strain is deposited under the entrustment number of NITE P-03333, and the SBT0320 strain It is deposited under the entrustment number of NITE P-03332, the SBT2785 strain is deposited under the entrustment number of NITE P-03328, and the SBT2992 strain is deposited under the entrustment number of NITE P-03364. The lactic acid bacteria or bifidobacteria of the present invention are not limited to the above-mentioned deposited lactic acid bacteria or bifidobacterium strains, and may be lactic acid bacteria or bifidobacterium strains substantially equivalent to these deposited lactic acid bacteria or bifidobacterium strains. Substantially equivalent strains of lactic acid bacteria or bifidobacteria belonging to Lactobacillus acidophilus, Lactobacillus helveticus, Lactobacillus salivarius, Lactobacillus salivarius subsp. salivarius, Lactococcus lactis subsp. lactis, Lactococcus lactis subsp. cocci, oral streptococci, Bifidobacterium longum, Bifidobacterium longum subsp. infantis, Bifidobacterium pseudolongum, lactic acid strains or bifidobacterium strains of Bifidobacterium thermophiles, and have the Lactobacillus strains or Bifidobacterium strains with the same high degree of improvement in joint function. "Lactobacillus strains or bifidobacterium strains having the same high degree of improvement in joint function as the deposited lactic acid bacteria strains or bifidobacterium strains" means, for example, the effect of promoting chondrocyte proliferation measured by the following steps 1)~3), Or the effect of inhibiting the production of inflammatory factors, cartilage matrix decomposition factors, pain factors, and nerve elongation factors determined by steps 4) to 7) of synoviocytes, and the effect of each deposited lactic acid bacteria strain or bifidobacterium strain Lactic acid bacteria strains or bifidobacterium strains that have no significant difference in the effect of promoting chondrocyte proliferation or inhibiting the production of inflammatory factors, cartilage matrix decomposition factors, pain factors, and nerve elongation factors caused by synoviocytes.

(促進軟骨細胞增殖之效果之評價方法) 1)將來自小鼠之軟骨前驅細胞株(ATDC5)以成為5,000cells/well的方式接種於96孔之平板細胞培養盤，於含5%(v/v)胎牛血清之DMEM培養基(Dulbecco's Modified Eagle's Medium)/Ham’s F-12混合培養基培養24小時。 2)去除全部的培養基後，更換為不含胎牛血清之DMEM培養基/Ham’s F-12混合培養基，以各種乳酸菌體破碎物或雙歧桿菌體破碎物最後濃度成為0.1mg/ml之方式添加至培養基，更培養48小時。 3)添加細胞增殖試藥並培養5小時後，測定於440nm之吸光度。就細胞增殖試藥而言，例如可使用WST-1(Roche Diagnostics K.K.)。 (抑制滑膜細胞所為之發炎因子、軟骨基質分解因子、疼痛因子、神經伸長因子之產生的效果) 4)將來自人類滑膜之細胞株(SW982)以成為100,000cells/well之方式接種至12孔之平板細胞培養盤，以含有10%(v/v)胎牛血清之Leibovitz’s L-15培養基培養1週。 5)除去全部的培養基後，替換為不含胎牛血清之Leibovitz’s L-15培養基，將human-IL-1β(Interleukin-1β)以最後濃度成為1ng/ml之方式添加至培養基，且以各種乳酸菌體破碎物或雙歧桿菌體破碎物之最後濃度成為1mg/ml之方式添加至培養基，更培養24小時。 6)除去全部培養基，使用從生物體樣本萃取總RNA用試藥，萃取全部的RNA，使用即時PCR(real-time PCR)用之反轉錄反應套組進行反轉錄反應。就從生物體樣本萃取總RNA用試藥而言，例如可使用Sepasol RNA 1 SuperG 試藥(Nacalai Tesque Inc.製)。就即時PCR用之反轉錄反應套組而言，例如可使用ReverTra Ace qPCR RT Master Mix(東洋紡公司製)。 7)使用獲得之cDNA，以含有Taq DNA polymerase之Realtime PCR用試藥進行即時 PCR，定量TNF-α(Tumor Necrosis Factor-α)、MMP-13(Matrix Metalloproteinase-13)、COX-2(Cyclooxygenase-2)、NGF(Nerve Growth Factor)基因之表現量。就含有Taq DNA polymerase之Realtime PCR用試藥而言，例如可使用THUNDERBIRD qPCR Mix(東洋紡公司製)。 (Evaluation method for the effect of promoting chondrocyte proliferation) 1) The cartilage precursor cell line (ATDC5) from the mouse was inoculated in a 96-well flat plate cell culture dish in a manner of 5,000 cells/well, in DMEM medium containing 5% (v/v) fetal bovine serum (Dulbecco's Modified Eagle's Medium)/Ham's F-12 mixed medium was cultured for 24 hours. 2) After removing all the medium, replace it with DMEM medium/Ham's F-12 mixed medium without fetal bovine serum, and add various broken lactic acid bacteria or broken bifidobacteria to a final concentration of 0.1mg/ml. Culture medium, further cultivated for 48 hours. 3) After adding the cell proliferation reagent and incubating for 5 hours, measure the absorbance at 440 nm. As a cell proliferation reagent, for example, WST-1 (Roche Diagnostics K.K.) can be used. (Inhibiting the production of inflammatory factors, cartilage matrix decomposition factors, pain factors, and nerve elongation factors produced by synoviocytes) 4) Inoculate the cell line (SW982) from human synovium into a 12-well plate cell culture plate in a manner of 100,000 cells/well, and culture it in Leibovitz's L-15 medium containing 10% (v/v) fetal bovine serum 1 week. 5) After removing all the medium, replace it with Leibovitz's L-15 medium without fetal bovine serum, add human-IL-1β (Interleukin-1β) to the medium at a final concentration of 1 ng/ml, and use various lactic acid bacteria The broken body or the broken body of bifidobacterium was added to the medium so that the final concentration of the broken body of bifidobacteria was 1 mg/ml, and cultured for 24 hours. 6) Remove all the medium, use reagents for extracting total RNA from biological samples, extract all RNA, and perform reverse transcription reaction using a real-time PCR (real-time PCR) reverse transcription reaction kit. As a reagent for extracting total RNA from a biological sample, for example, Sepasol RNA 1 SuperG reagent (manufactured by Nacalai Tesque Inc.) can be used. As a reverse transcription reaction kit for real-time PCR, for example, ReverTra Ace qPCR RT Master Mix (manufactured by Toyobo Co., Ltd.) can be used. 7) Using the obtained cDNA, perform real-time PCR with reagents for Realtime PCR containing Taq DNA polymerase to quantify TNF-α (Tumor Necrosis Factor-α), MMP-13 (Matrix Metalloproteinase-13), COX-2 (Cyclooxygenase- 2), NGF (Nerve Growth Factor) gene expression. As a reagent for realtime PCR containing Taq DNA polymerase, for example, THUNDERBIRD qPCR Mix (manufactured by Toyobo Co., Ltd.) can be used.

本發明之乳酸菌或雙歧桿菌，在藉由上述步驟1)~3)進行促進軟骨細胞增殖效果之評價時，宜為經測定之促進細胞增殖效果相較於未添加乳酸菌株或雙歧桿菌株之控制組中之促進軟骨細胞增殖效果係1.5倍以上、更宜為2倍以上。此外，上述「經測定之促進細胞增殖效果」係指上述步驟1)~3)後所測定之吸光度之值的大小。 此外，本發明之乳酸菌或雙歧桿菌係在藉由上述步驟4)~7)來評價抑制滑膜細胞所致之發炎因子、軟骨基質分解因子、疼痛因子、神經伸長因子之產生的效果時，宜為經測定之抑制滑膜細胞所致之發炎因子、軟骨基質分解因子、疼痛因子、神經伸長因子之產生的效果，相較於未添加乳酸菌株或雙歧桿菌株之控制組中之抑制滑膜細胞所致之發炎因子、軟骨基質分解因子、疼痛因子、神經伸長因子之產生的效果，為1.5倍以上，更宜為2倍以上，進一步宜為3倍以上。此外，上述「經測定之抑制滑膜細胞所致之發炎因子、軟骨基質分解因子、疼痛因子、神經伸長因子之產生的效果」係指上述步驟4)~7)後所測定之表現量。表現量越小，則抑制滑膜細胞所致之發炎因子、軟骨基質分解因子、疼痛因子、神經伸長因子之產生的效果越大。例如試驗例2中，乳酸乳球菌乳酸亞種 SBT0625菌株係相較於對照(PBS)，發炎因子為5分之1以下，且相較於對照，具有5倍以上之發炎抑制效果。 此外，並不限定於上述評價方法，能夠採用所屬技術領域具通常知識者公知的促進軟骨細胞增殖效果之評價方法或抑制滑膜細胞所致之發炎因子、軟骨基質分解因子、疼痛因子、神經伸長因子之產生的效果的評價方法，來評價促進軟骨細胞增殖效果或抑制滑膜細胞所致之發炎因子、軟骨基質分解因子、疼痛因子、神經伸長因子之產生的效果。 此外，實質上同等之乳酸菌株或雙歧桿菌株更具有其16S核糖體RNA基因之鹼基序列係與上述寄存乳酸菌株或雙歧桿菌株之16S核糖體RNA基因之鹼基序列為98%以上、宜為99%以上、更宜為100%的相同性，且宜為具有與上述寄存乳酸菌株或雙歧桿菌株相同的菌學性質。另外，本發明之乳酸菌或雙歧桿菌，在不損害本發明之效果的情況下，亦可為從寄存乳酸菌株或雙歧桿菌株、或者與此等實質上同等之乳酸菌株或雙歧桿菌株，藉由突變處理、基因重組、自然突變株之選擇等所培育而得的乳酸菌株或雙歧桿菌株。 When the lactic acid bacteria or bifidobacteria of the present invention are evaluated for the effect of promoting chondrocyte proliferation by the above steps 1) to 3), it is preferable that the measured effect of promoting cell proliferation is compared with that of no lactic acid bacteria strain or bifidobacterium strain The effect of promoting chondrocyte proliferation in the control group is more than 1.5 times, more preferably more than 2 times. In addition, the above-mentioned "measured cell proliferation-promoting effect" refers to the magnitude of the absorbance value measured after the above steps 1) to 3). In addition, when the lactic acid bacteria or bifidobacteria of the present invention are used to evaluate the effect of inhibiting the production of synoviocyte-induced inflammatory factors, cartilage matrix decomposition factors, pain factors, and nerve elongation factors through the above steps 4) to 7), It is preferably the effect of inhibiting the production of inflammatory factors, cartilage matrix decomposition factors, pain factors, and nerve elongation factors caused by synoviocytes, compared with the inhibition of synoviocytes in the control group without adding lactic acid bacteria strains or bifidobacterium strains. The production effects of inflammatory factors, cartilage matrix decomposition factors, pain factors, and nerve elongation factors caused by theca cells are more than 1.5 times, more preferably more than 2 times, and more preferably more than 3 times. In addition, the above "measured effects of inhibiting the production of synoviocyte-induced inflammatory factors, cartilage matrix decomposition factors, pain factors, and nerve elongation factors" refers to the expression levels measured after the above steps 4) to 7). The smaller the expression level, the greater the effect of inhibiting the production of inflammatory factors, cartilage matrix decomposition factors, pain factors, and nerve elongation factors caused by synoviocytes. For example, in Test Example 2, compared with the control (PBS), the Lactococcus lactis subsp. lactic acid SBT0625 strain had less than 1/5 of the inflammatory factor, and compared with the control, it had more than 5 times the anti-inflammatory effect. In addition, it is not limited to the above-mentioned evaluation methods, and evaluation methods known to those skilled in the art for promoting the proliferation of chondrocytes or inhibiting inflammatory factors, cartilage matrix decomposition factors, pain factors, and nerve elongation caused by synoviocytes can be used. The evaluation method of the effect of factor production is to evaluate the effect of promoting the proliferation of chondrocytes or inhibiting the production of inflammatory factors, cartilage matrix decomposition factors, pain factors, and nerve elongation factors caused by synoviocytes. In addition, the 16S ribosomal RNA gene base sequence of the substantially identical lactic acid bacteria or bifidobacterium strains is more than 98% of the base sequence of the 16S ribosomal RNA gene of the above-mentioned deposited lactic acid bacteria or bifidobacterium strains , preferably more than 99%, more preferably 100% identity, and preferably have the same bacteriological properties as the above-mentioned deposited lactic acid bacteria strains or bifidobacteria strains. In addition, the lactic acid bacteria or bifidobacteria of the present invention may be a lactic acid bacteria strain or a bifidobacterium strain derived from a deposit, or a lactic acid bacteria strain or a bifidobacterium strain substantially equivalent to these without impairing the effect of the present invention. , lactic acid bacteria strains or bifidobacterium strains bred by mutation treatment, genetic recombination, selection of natural mutant strains, etc.

(有效成分之攝取量) 本發明之乳酸菌或雙歧桿菌之菌體或培養物之攝取量，只要是能藉由促進軟骨細胞之增殖的作用、或者抑制滑膜細胞所致之發炎因子、軟骨基質分解因子、疼痛因子、神經伸長因子之產生的作用而展現出關節功能改善作用的量便沒有特別之限制，配合製造的容易性或者適宜之1日攝取量適當地調節即可。本發明之投予對象係沒有特別限定，能夠對於人類投予，但投予對象亦可為人以外的動物(例如狗、貓、馬、牛或兔等)。投予對象為人時，可對於未滿20歲之未成年、成人、男女、或65歲以上之高齡者等投予。本發明之乳酸菌或雙歧桿菌之菌體或培養物之攝取量係考慮投予對象者之症狀、年齡、及性別等各別決定，通常為成人之情況，以乳酸菌或雙歧桿菌之培養物等能攝取10~200g、或者其菌體能攝取0.1~5,000mg之方式來調整摻合量等即可。本發明之乳酸菌或雙歧桿菌之菌體或培養物可直接經口攝取，在摻合至飲食品、營養組成物、飼料及口服用醫藥等之情況，以成為上述攝取量的方式來調整摻合量即可。藉由以如此方式攝取，可發揮期望的效果。 投予對象可為罹患以退化性膝關節炎為代表之退化性關節炎或類風濕性關節炎等各種關節疾病之患者，或者罹患的風險高之對象，亦可為尚未患病之健康的對象。 (Intake of active ingredients) The intake of lactic acid bacteria or bifidobacteria of the present invention or the culture of the bacteria, as long as it can promote the proliferation of chondrocytes, or inhibit the inflammatory factors caused by synoviocytes, cartilage matrix decomposition factors, pain factors, There is no particular limitation on the amount of nerve elongation factor that exhibits the effect of improving joint function, and it can be adjusted appropriately according to the ease of manufacture or the appropriate daily intake. The administration object of the present invention is not particularly limited, and it can be administered to humans, but the administration object can also be animals other than humans (such as dogs, cats, horses, cows, or rabbits). When the target of administration is human, it can be administered to minors under 20 years old, adults, men and women, or elderly persons over 65 years old. The intake of the bacteria or cultures of lactic acid bacteria or bifidobacteria of the present invention is determined by taking into account the symptoms, age, and sex of the subject to be administered. Usually, in the case of adults, cultures of lactic acid bacteria or bifidobacteria are used The blending amount can be adjusted so that 10~200g can be ingested, or 0.1~5,000mg can be ingested by the bacteria. The bacterial cells or cultures of lactic acid bacteria or bifidobacteria of the present invention can be ingested directly orally, and when blended into food and beverages, nutritional compositions, feeds, and oral medicines, etc., the blending amount is adjusted so that the above-mentioned intake amount can be achieved. Just add the amount. By ingesting it in this way, a desired effect can be exerted. The subject of administration can be a patient suffering from various joint diseases such as degenerative arthritis represented by degenerative knee arthritis or rheumatoid arthritis, or a subject with a high risk of suffering from the disease, or a healthy subject who has not yet suffered from the disease .

(關於本發明之乳酸菌或雙歧桿菌之使用於飲食品及醫藥品的方法) 本發明之乳酸菌或雙歧桿菌之菌體或培養物，可各別單獨或者任意地組合，直接作為關節功能改善用組成物來使用，亦可在不喪失藉由促進軟骨細胞之增殖的作用、或者抑制滑膜細胞所致之發炎因子、軟骨基質分解因子、疼痛因子、神經伸長因子之產生的作用而得之關節功能改善作用的範圍內，因應需求依循通常方法，製劑化成為粉末劑、顆粒劑、錠劑、膠囊劑、飲料劑等來使用。此外，本發明之乳酸菌或雙歧桿菌之菌體或培養物、或者經製劑化後，亦可摻合至營養劑或奶粉、乳飲料、乳酸菌飲料、發酵乳、軟飲料、起司、人造奶油、乳油(cream)、布丁、果凍、威化餅等飲食品、營養組成物、飼料及醫藥品中。 本發明之乳酸菌或雙歧桿菌之菌體或培養物亦可與其他之飲食品、飼料及醫藥品中通常含有之安定劑或糖類、脂質、香料、維生素、礦物質、類黃酮、多酚等原材料一起使用。 此外，本發明之飲食品亦可作為功能性表現食品、特定保健用食品、營養機能食品、或美容用食品來使用。 (About the method of using the lactic acid bacteria or bifidobacteria of the present invention in food and beverages and pharmaceuticals) The bacterial cells or cultures of lactic acid bacteria or bifidobacteria of the present invention can be used alone or in any combination, directly as a composition for improving joint function, and can also be used without losing the effect of promoting the proliferation of chondrocytes, Or within the scope of improving joint function obtained by inhibiting the production of inflammatory factors, cartilage matrix decomposition factors, pain factors, and nerve elongation factors caused by synoviocytes, according to the needs, follow the usual method and prepare powders and granules. Tablets, lozenges, capsules, beverages, etc. In addition, the bacterial cells or cultures of lactic acid bacteria or bifidobacteria of the present invention, or after formulation, can also be blended into nutritional supplements or milk powder, milk drinks, lactic acid bacteria drinks, fermented milk, soft drinks, cheese, margarine, In food and drink such as cream, pudding, jelly, wafer, nutritional composition, feed and pharmaceuticals. The bacteria or cultures of lactic acid bacteria or bifidobacteria of the present invention can also be mixed with stabilizers or sugars, lipids, spices, vitamins, minerals, flavonoids, polyphenols, etc. Raw materials are used together. In addition, the food and drink of the present invention can also be used as food for functional expression, food for specific health use, food for nutritional function, or food for beauty use.

在製劑化時，可使用通常使用之填充劑、增量劑、黏合劑、崩散劑、界面活性劑、潤滑劑等稀釋劑或賦形劑。就賦形劑而言，可添加例如蔗糖、乳糖、澱粉、結晶性纖維素、甘露醇、輕質無水矽酸、鋁酸鎂、合成矽酸鋁、偏矽酸鋁酸鎂、碳酸鈣、碳酸氫鈉、磷酸氫鈣、羧基甲基纖維素鈣等之1種或組合2種以上。During formulation, commonly used diluents or excipients such as fillers, extenders, binders, disintegrating agents, surfactants, lubricants, etc. can be used. In terms of excipients, for example, sucrose, lactose, starch, crystalline cellulose, mannitol, light anhydrous silicic acid, magnesium aluminate, synthetic aluminum silicate, magnesium aluminum metasilicate, calcium carbonate, carbonic acid can be added. Sodium hydrogen phosphate, calcium hydrogen phosphate, carboxymethylcellulose calcium, etc. 1 type or a combination of 2 or more types.

以下揭示實施例、試驗例，針對本發明詳細地進行說明，但本發明不因此等而有所限定。此外，本說明書中，但在沒有特別說明的情況，%表示質量%。 [實施例] Examples and test examples are disclosed below, and the present invention will be described in detail, but the present invention is not limited thereto. In addition, in this specification, unless otherwise specified, % represents mass %. [Example]

(實施例1) 將嗜酸乳桿菌(Lactobacillus acidophilus)SBT2062菌株、瑞士乳桿菌(Lactobacillus helveticus)SBT2161菌株、SBT2171菌株、唾液乳桿菌(Lactobacillus salivarius)SBT2687菌株、SBT2651菌株、唾液乳桿菌唾液亞種(Lactobacillus salivarius subsp. salivarius)SBT2670菌株、口腔鏈球菌(Streptococcus oralis)SBT0320菌株，藉由經121℃、15分鐘之滅菌處理的MRS broth(DIFCO公司製)，使各個菌株每個進行37℃、16小時之3代以上的培養予以活化。將其各別接種3%(v/v)至相同的培養基，於37℃培養16小時後，藉由離心分離分離各個菌體。菌體係以滅菌生理食鹽水清洗2次、以超純水清洗1次後，進行冷凍乾燥，獲得嗜酸乳桿菌(Lactobacillus acidophilus)SBT2062菌株、瑞士乳桿菌(Lactobacillus helveticus)SBT2161菌株、SBT2171菌株、唾液乳桿菌(Lactobacillus salivarius)SBT2687菌株、SBT2651菌株、唾液乳桿菌唾液亞種(Lactobacillus salivarius subsp. salivarius)SBT2670菌株、口腔鏈球菌(Streptococcus oralis)SBT0320菌株的菌體(實施例品1)。以如此方式獲得之嗜酸乳桿菌(Lactobacillus acidophilus)SBT2062菌株、瑞士乳桿菌(Lactobacillus helveticus)SBT2161菌株、SBT2171菌株、唾液乳桿菌(Lactobacillus salivarius)SBT2687菌株、SBT2651菌株、唾液乳桿菌唾液亞種(Lactobacillus salivarius subsp. salivarius)SBT2670菌株、口腔鏈球菌(Streptococcus oralis)SBT0320菌株的菌體，可直接作為本發明之具有關節功能改善作用的乳酸菌來使用。將實施例品1之菌體，使用EZ-Beads (AMR Inc.)進行物理性的破碎，使用於以下的試驗。 (Example 1) Lactobacillus acidophilus SBT2062 strain, Lactobacillus helveticus SBT2161 strain, SBT2171 strain, Lactobacillus salivarius SBT2687 strain, SBT2651 strain, Lactobacillus salivarius subsp. ) SBT2670 strain and Streptococcus oralis SBT0320 strain were sterilized by MRS broth (manufactured by DIFCO) at 121°C for 15 minutes, and each strain was sterilized for more than 3 generations at 37°C for 16 hours. Culture is activated. They were respectively inoculated at 3% (v/v) into the same medium, and after culturing at 37° C. for 16 hours, each bacterial cell was isolated by centrifugation. The bacterial system was washed twice with sterilized saline and once with ultrapure water, and then freeze-dried to obtain Lactobacillus acidophilus SBT2062 strain, Lactobacillus helveticus SBT2161 strain, SBT2171 strain, saliva Lactobacillus salivarius SBT2687 strain, SBT2651 strain, Lactobacillus salivarius subsp. salivarius SBT2670 strain, Streptococcus oralis SBT0320 strain (Example 1). Lactobacillus acidophilus SBT2062 strain, Lactobacillus helveticus SBT2161 strain, SBT2171 strain, Lactobacillus salivarius SBT2687 strain, SBT2651 strain, Lactobacillus helveticus subsp. Salivarius subsp. salivarius) SBT2670 bacterial strain, oral streptococcus (Streptococcus oralis) SBT0320 bacterial strain can be directly used as the lactic acid bacteria with joint function improving effect of the present invention. The bacterial cells of Example 1 were physically crushed using EZ-Beads (AMR Inc.), and used in the following tests.

(實施例2) 將乳酸乳球菌乳酸亞種(Lactococcus lactis subsp. lactis)SBT0625菌株、乳酸乳球菌乳脂亞種(Lactococcus lactis subsp. cremoris)SBT11373菌株、勞氏乳球菌(Lactococcus laudensis)SBT11178菌株，藉由對於經121℃、15分鐘之滅菌處理的M17培養基(DIFCO公司製)，以最後濃度成為0.5%之方式添加了經121℃、15分鐘之滅菌處理的乳糖溶液而得的培養基，使各個菌株每個進行30℃、16小時至24小時之3代以上的培養予以活化。將其各別接種3%(v/v)至相同的培養基，於30℃培養16小時至24小時後，藉由離心分離分離各個菌體。菌體係以滅菌生理食鹽水清洗2次、以超純水清洗1次後，進行冷凍乾燥，獲得乳酸乳球菌乳酸亞種(Lactococcus lactis subsp. lactis)SBT0625菌株、乳酸乳球菌乳脂亞種(Lactococcus lactis subsp. cremoris)SBT11373菌株、勞氏乳球菌(Lactococcus laudensis)SBT11178菌株之菌體(實施例品2)。以如此方式獲得之乳酸乳球菌乳酸亞種(Lactococcus lactis subsp. lactis)SBT0625菌株、乳酸乳球菌乳脂亞種(Lactococcus lactis subsp. cremoris)SBT11373菌株、勞氏乳球菌(Lactococcus laudensis)SBT11178菌株之菌體可直接作為本發明之具有關節功能改善作用的乳酸菌來使用。將實施例品2之菌體，使用EZ-Beads (AMR Inc.)進行物理性的破碎，使用於以下的試驗。 (Example 2) Lactococcus lactis subsp. lactis SBT0625 strain, Lactococcus lactis subsp. cremoris SBT11373 strain, Lactococcus laudensis SBT11178 strain, by heating at 121°C M17 medium (manufactured by DIFCO) sterilized for 15 minutes was added with a lactose solution sterilized at 121°C for 15 minutes so that the final concentration became 0.5%, and each strain was subjected to 30°C , 16 hours to 24 hours for more than 3 passages of culture to be activated. They were respectively inoculated with 3% (v/v) into the same medium, cultured at 30° C. for 16 hours to 24 hours, and then separated by centrifugation. The bacterial system was washed twice with sterilized saline and once with ultrapure water, and then freeze-dried to obtain Lactococcus lactis subsp. lactis SBT0625 strain, Lactococcus lactis subsp. subsp. cremoris) SBT11373 strain, Lactococcus laudensis (Lactococcus laudensis) SBT11178 strain (Example 2). Lactococcus lactis subsp. lactis SBT0625 strain, Lactococcus lactis subsp. cremoris SBT11373 strain, Lactococcus laudensis SBT11178 strain obtained in this way It can be directly used as the lactic acid bacteria with joint function improving effect of the present invention. The bacterial cells of Example 2 were physically crushed using EZ-Beads (AMR Inc.) and used in the following tests.

(實施例3) 將長雙歧桿菌(Bifidobacterium longum)SBT2928菌株、長雙歧桿菌嬰兒亞種(Bifidobacterium longum subsp. infantis)SBT2785菌株、假長雙歧桿菌(Bifidobacterium pseudolongum)SBT2922菌株、嗜熱雙歧桿菌(Bifidobacterium thermophilum)SBT2992菌株，藉由對於經115℃、15分鐘之滅菌處理的GAM培養基(日水製藥公司製)，以最後濃度成為1%之方式添加了經115℃、15分鐘之滅菌處理的葡萄糖溶液而得的培養基，使各個菌株每個進行37℃、16小時至21小時之3代以上的培養予以活化。將其各別接種3%(v/v)至相同的培養基，於37℃培養16小時至21小時後，藉由離心分離分離各個菌體。菌體係以滅菌生理食鹽水清洗2次、以超純水清洗1次後，進行冷凍乾燥，獲得長雙歧桿菌(Bifidobacterium longum)SBT2928菌株、長雙歧桿菌嬰兒亞種(Bifidobacterium longum subsp. infantis)SBT2785菌株、假長雙歧桿菌(Bifidobacterium pseudolongum)SBT2922菌株、嗜熱雙歧桿菌(Bifidobacterium thermophilum)SBT2992菌株之菌體(實施例品3)。以如此方式獲得之長雙歧桿菌(Bifidobacterium longum)SBT2928菌株、長雙歧桿菌嬰兒亞種(Bifidobacterium longum subsp. infantis)SBT2785菌株、假長雙歧桿菌(Bifidobacterium pseudolongum)SBT2922菌株、嗜熱雙歧桿菌(Bifidobacterium thermophilum)SBT2992菌株之菌體，可直接作為本發明之具有關節功能改善作用之雙歧桿菌使用。將實施例品3之菌體，使用EZ-Beads (AMR Inc.)進行物理性的破碎，使用於以下之試驗。 (Example 3) Bifidobacterium longum SBT2928 strain, Bifidobacterium longum subsp. infantis SBT2785 strain, Bifidobacterium pseudolongum SBT2922 strain, Bifidobacterium thermophilum The SBT2992 strain was obtained by adding a glucose solution sterilized at 115°C for 15 minutes to a GAM medium (manufactured by Nissui Pharmaceutical Co., Ltd.) sterilized at 115°C for 15 minutes to a final concentration of 1%. The culture medium was used to activate each strain by culturing at 37° C. for 16 hours to 21 hours for more than 3 generations. They were respectively inoculated with 3% (v/v) into the same medium, cultured at 37° C. for 16 hours to 21 hours, and then separated by centrifugation. The bacterial system was washed twice with sterilized saline and once with ultrapure water, and then freeze-dried to obtain Bifidobacterium longum SBT2928 strain and Bifidobacterium longum subsp. infantis The cells of SBT2785 strain, Bifidobacterium pseudolongum SBT2922 strain, and Bifidobacterium thermophilum SBT2992 strain (Example 3). Thus obtained Bifidobacterium longum SBT2928 strain, Bifidobacterium longum subsp. infantis SBT2785 strain, Bifidobacterium pseudolongum SBT2922 strain, Bifidobacterium thermophilic (Bifidobacterium thermophilum) SBT2992 bacterial strain can be directly used as the bifidobacterium having joint function improving effect of the present invention. The bacteria of Example 3 were physically crushed using EZ-Beads (AMR Inc.) and used in the following experiments.

(比較例1) 將雪印惠乳(股)公司保有之融合魏斯氏菌(Weissella confusa)No.1菌株，藉由經121℃、15分鐘之滅菌處理而得的MRS broth(DIFCO公司製)，進行37℃、16小時之3代以上的培養予以活化。將其各別接種3%(v/v)至相同的培養基，於37℃培養16小時後，藉由離心分離分離各個菌體。菌體係以滅菌生理食鹽水清洗2次、以超純水清洗1次後，進行冷凍乾燥，獲得融合魏斯氏菌(Weissella confusa)No.1菌株之菌體(比較例品1)。將比較例品1之菌體使用EZ-Beads (AMR Inc.)進行物理性的破碎，使用於以下之試驗。 (comparative example 1) The No. 1 strain of Weissella confusa (Weissella confusa) retained by Snow India Co., Ltd. was sterilized at 121°C for 15 minutes with MRS broth (manufactured by DIFCO) at 37°C. Cultures of more than 3 passages in 16 hours were activated. They were respectively inoculated at 3% (v/v) into the same medium, and after culturing at 37° C. for 16 hours, each bacterial cell was isolated by centrifugation. The bacteria system was washed twice with sterilized saline and once with ultrapure water, and then freeze-dried to obtain bacteria fused with Weissella confusa No. 1 strain (comparative example 1). The cells of Comparative Example 1 were physically crushed using EZ-Beads (AMR Inc.) and used in the following experiments.

(比較例2) 將雪印惠乳(股)公司保有之戊糖片球菌(Pediococcus pentosaceus)No.1菌株，藉由經121℃、15分鐘之滅菌處理而得之MRS broth(DIFCO公司製)，進行37℃、16小時之3代以上的培養予以活化。將其各別接種3%(v/v)至相同的培養基，於37℃培養16小時後，藉由離心分離分離各個菌體。菌體以滅菌生理食鹽水清洗2次、以超純水清洗1次後，進行冷凍乾燥，獲得戊糖片球菌(Pediococcus pentosaceus)No.1菌株之菌體(比較例品2)。將比較例品2之菌體，使用EZ-Beads (AMR Inc.)進行物理性的破碎，使用於以下之試驗。 (comparative example 2) The No. 1 strain of Pediococcus pentosaceus retained by Snow Brand Huiru Co., Ltd. was subjected to MRS broth (manufactured by DIFCO), which was sterilized at 121°C for 15 minutes, and subjected to 37°C, 16 Cultures of more than 3 passages per hour are activated. They were respectively inoculated at 3% (v/v) into the same medium, and after culturing at 37° C. for 16 hours, each bacterial cell was isolated by centrifugation. The cells were washed twice with sterilized saline and once with ultrapure water, and then freeze-dried to obtain the cells of Pediococcus pentosaceus No. 1 strain (Comparative Example 2). The cells of Comparative Example 2 were physically crushed using EZ-Beads (AMR Inc.) and used in the following tests.

(比較例3) 將雪印惠乳(股)公司保有之腸膜明串珠菌(Leuconostoc mesenteroides)No.1菌株，藉由經121℃、15分鐘之滅菌處理而得的MRS broth(DIFCO公司製)，進行25℃、24小時之3代以上的培養予以活化。將其各別接種3%(v/v)至相同的培養基，於25℃培養24小時後，藉由離心分離分離各個菌體。菌體以滅菌生理食鹽水清洗2次、以超純水清洗1次後，進行冷凍乾燥，獲得腸膜明串珠菌(Leuconostoc mesenteroides)No.1菌株之菌體(比較例品3)。將比較例品3之菌體，使用EZ-Beads (AMR Inc.)進行物理性的破碎，使用於以下之試驗。 (comparative example 3) Leuconostoc mesenteroides No. 1 strain retained by Snow India Huiru Co., Ltd. was subjected to 25°C, Cultures of more than 3 passages in 24 hours were activated. They were respectively inoculated at 3% (v/v) to the same medium, and after culturing at 25° C. for 24 hours, each bacterial cell was isolated by centrifugation. The cells were washed twice with sterilized saline and once with ultrapure water, and then freeze-dried to obtain the cells of Leuconostoc mesenteroides No. 1 strain (Comparative Example 3). The cells of Comparative Example 3 were physically crushed using EZ-Beads (AMR Inc.) and used in the following tests.

(試驗例1) 調查實施例品3之嗜熱雙歧桿菌(Bifidobacterium thermophilum)SBT2992菌株之菌體破碎物之促進軟骨細胞增殖效果。此外，為了比較，調查比較例品1之融合魏斯氏菌(Weissella confusa)No.1菌株之菌體破碎物之促進軟骨細胞增殖效果。 將來自小鼠之軟骨前驅細胞株(ATDC5)以成為5,000cells/well之方式接種於96孔之平板細胞培養盤，於含5%(v/v)胎牛血清之DMEM培養基/Ham’s F-12混合培養基，在37℃、5%CO 2環境下培養24小時。之後，除去全部的培養基，以不含胎牛血清之DMEM培養基/Ham’s F-12培養基予以清洗並替換培養基，以實施例品3之嗜熱雙歧桿菌(Bifidobacterium thermophilum)SBT2992菌株與比較例品1之融合魏斯氏菌(Weissella confusa)No.1菌株之菌體破碎物各別之最後濃度成為0.1mg/ml的方式添加至培養基，培養48小時。之後，去除全部的培養基，將細胞增殖試藥WST-1(Roche Diagnostics K.K.)以在培養基中含有10分之1的量的方式添加後，培養5小時，使用盤式分析儀，測定440nm之吸光度。WST-1係因為活細胞之代謝活性而還原為甲臘(formazan)色素，甲臘色素量係與具有代謝活性之細胞數目成正比。因此，將反映甲臘色素量之吸光度的值作為促進軟骨細胞增殖效果的指標。 (Test Example 1) The chondrocyte growth-promoting effect of the crushed bacteria of Bifidobacterium thermophilum (Bifidobacterium thermophilum) SBT2992 strain of Example 3 was investigated. In addition, for the sake of comparison, the chondrocyte growth-promoting effect of the chondrocyte proliferation-promoting effect of the bacterial cell crushing product fused with Weissella confusa No. 1 strain of Comparative Example 1 was investigated. The cartilage precursor cell line (ATDC5) from the mouse was inoculated in a 96-well plate cell culture dish at a rate of 5,000 cells/well in DMEM medium/Ham's F-12 containing 5% (v/v) fetal bovine serum Mix the medium and incubate for 24 hours at 37°C, 5% CO 2 environment. Afterwards, remove all the culture medium, wash and replace the culture medium with the DMEM medium/Ham's F-12 medium that does not contain fetal bovine serum, with the bifidobacterium thermophilum (Bifidobacterium thermophilum) SBT2992 bacterial strain of embodiment product 3 and comparative example product 1 The crushed cells of the fused Weissella confusa No. 1 strain were added to the culture medium so that the final concentration of each was 0.1 mg/ml, and cultured for 48 hours. Thereafter, all the medium was removed, and the cell proliferation reagent WST-1 (Roche Diagnostics KK) was added so as to contain 1/10 of the amount in the medium, cultured for 5 hours, and the absorbance at 440 nm was measured using a disk analyzer. . WST-1 is reduced to formazan pigment due to the metabolic activity of living cells, and the amount of formazan is proportional to the number of metabolically active cells. Therefore, the value of absorbance reflecting the amount of formazan was used as an indicator of the effect of promoting chondrocyte proliferation.

[表1] 菌株名 吸光度(440nm) 對照(PBS) 0.626±0.021 融合魏斯氏菌(Weissella confusa)No.1菌株 0.632±0.038 嗜熱雙歧桿菌(Bifidobacterium thermophilum)SBT2992菌株 1.269±0.029※ 數值係表示平均值±標準差(n=4) ※表示與對照(PBS)相比較具有顯著差異(p＜0.05) [Table 1] strain name Absorbance (440nm) Control (PBS) 0.626±0.021 Fusion Weissella confusa No.1 strain 0.632±0.038 Bifidobacterium thermophilum SBT2992 strain 1.269±0.029※ Values represent mean ± standard deviation (n=4) ※Indicates a significant difference compared with the control (PBS) (p<0.05)

其結果，添加了嗜熱雙歧桿菌(Bifidobacterium thermophilum)SBT2992菌株之菌體破碎物的情況，相較於對照(PBS)，軟骨前驅細胞之細胞數目係顯著地增加。因此，可知本發明之嗜熱雙歧桿菌(Bifidobacterium thermophilum)SBT2992菌株的菌體破碎物具有促進軟骨細胞之增殖的效果。另一方面，比較例品1之融合魏斯氏菌(Weissella confusa)No.1菌株的菌體破碎物係未展現促進軟骨細胞之增殖的效果。As a result, the number of cartilage precursor cells was significantly increased in the case of adding the crushed body of Bifidobacterium thermophilum (Bifidobacterium thermophilum) SBT2992 strain compared to the control (PBS). Therefore, it can be seen that the cell crushed product of the Bifidobacterium thermophilum SBT2992 strain of the present invention has the effect of promoting the proliferation of chondrocytes. On the other hand, the crushed cell line of Comparative Example 1 fused with Weissella confusa No. 1 strain did not exhibit the effect of promoting the proliferation of chondrocytes.

(試驗例2) 調查實施例品1之嗜酸乳桿菌(Lactobacillus acidophilus)SBT2062菌株、瑞士乳桿菌(Lactobacillus helveticus)SBT2161菌株、SBT2171菌株、唾液乳桿菌(Lactobacillus salivarius)SBT2687菌株、SBT2651菌株、唾液乳桿菌唾液亞種(Lactobacillus salivarius subsp. salivarius)SBT2670菌株、口腔鏈球菌(Streptococcus oralis)SBT0320菌株、實施例品2之乳酸乳球菌乳酸亞種(Lactococcus lactis subsp. lactis)SBT0625菌株、乳酸乳球菌乳脂亞種(Lactococcus lactis subsp. cremoris)SBT11373菌株、勞氏乳球菌(Lactococcus laudensis)SBT11178菌株、實施例品3之長雙歧桿菌(Bifidobacterium longum)SBT2928菌株、嗜熱雙歧桿菌(Bifidobacterium thermophilum)SBT2992菌株之菌體破碎物之抑制滑膜細胞所致之發炎因子之產生的效果。此外，為了比較，調查比較例品2之戊糖片球菌(Pediococcus pentosaceus)No.1菌株之菌體破碎物之抑制滑膜細胞所致之發炎因子之產生的效果。 將來自人類滑膜之細胞株(SW982)以成為100,000cells/well 之方式接種至12孔之平板細胞培養盤，以含有10%(v/v)胎牛血清之Leibovitz’s L-15培養基於37℃、5%CO 2環境下培養1週。之後，去除全部的培養基，以不含胎牛血清之Leibovitz’s L-15培養基進行清洗並替換培養基。將human-IL-1β(Interleukin-1β)以最後濃度成為1ng/ml之方式添加至培養基，將本發明之菌體破碎物以最後濃度成為1mg/ml之方式添加至培養基，更培養24小時。之後，使用Sepasol RNA 1 SuperG 試藥(Nacalai Tesque Inc製)從培養後之細胞萃取全部的RNA。反轉錄反應係使用ReverTra Ace qPCR RT Master Mix(東洋紡公司製)。使用獲得之cDNA，藉由THUNDERBIRD qPCR Mix(東洋紡公司製)進行即時PCR，定量為發炎因子之TNF-α(Tumor Necrosis Factor-α)之基因表現量。此外，使用GAPDH(Glyceraldehyde-3-phosphate dehydrogenase)基因之表現量作為用以評價基因表現量的內部標準，在分析中，對於TNF-α使用序列表序列編號1、2之引子，對於GAPDH使用序列表序列編號3、4之引子。 (Experiment 2) The Lactobacillus acidophilus (Lactobacillus acidophilus) SBT2062 strain, Lactobacillus helveticus (Lactobacillus helveticus) SBT2161 strain, SBT2171 strain, Lactobacillus salivarius (Lactobacillus salivarius) SBT2687 strain, SBT2651 strain, saliva milk Lactobacillus salivarius subsp. salivarius SBT2670 strain, Streptococcus oralis SBT0320 strain, Lactococcus lactis subsp. lactis SBT0625 strain of Example 2, Lactococcus lactis subsp. Cremoris) SBT11373 strain, Lactococcus laudensis SBT11178 strain, Bifidobacterium longum SBT2928 strain of Example 3, Bifidobacterium thermophilum SBT2992 strain The effect of the disrupted bacteria inhibits the production of inflammatory factors caused by synoviocytes. In addition, for comparison, the effect of inhibiting the production of inflammatory factors by synoviocytes of the crushed bacteria of Pediococcus pentosaceus (Pediococcus pentosaceus) No. 1 strain of Comparative Example 2 was investigated. The cell line (SW982) from human synovium was inoculated into a 12-well plate cell culture plate in a manner of 100,000 cells/well, and cultured in Leibovitz's L-15 containing 10% (v/v) fetal bovine serum at 37°C , 5% CO 2 environment for 1 week. Thereafter, all the medium was removed, washed with Leibovitz's L-15 medium without fetal bovine serum, and the medium was replaced. Human-IL-1β (Interleukin-1β) was added to the medium at a final concentration of 1 ng/ml, and the disrupted bacterial cells of the present invention were added to the medium at a final concentration of 1 mg/ml, and cultured for 24 hours. Thereafter, all RNA was extracted from the cultured cells using Sepasol RNA 1 SuperG reagent (manufactured by Nacalai Tesque Inc). For the reverse transcription reaction, ReverTra Ace qPCR RT Master Mix (manufactured by Toyobo Co., Ltd.) was used. Using the obtained cDNA, real-time PCR was performed with THUNDERBIRD qPCR Mix (manufactured by Toyobo Co., Ltd.), and the gene expression level of TNF-α (Tumor Necrosis Factor-α), which is an inflammatory factor, was quantified. In addition, the expression of GAPDH (Glyceraldehyde-3-phosphate dehydrogenase) gene was used as an internal standard for evaluating gene expression. In the analysis, the primers of sequence number 1 and 2 of the sequence table were used for TNF-α, and the sequence number 2 was used for GAPDH. The primers of sequence numbers 3 and 4 in the list.

[表2] 序列編號   鹼基序列(5'=3') 1 前置 GAG GCC AAG CCC TGG TAT G 2 反置 CGG GCC GAT TGA TCT CAG C 3 前置 CTG GGC TAC ACT GAG CAC C 4 反置 AAG TGG TCG TTG AGG GCA ATG [Table 2] serial number Base sequence (5'=3') 1 Front GAG GCC AAG CCC TGG TAT G 2 reverse CGG GCC GAT TGA TCT CAG C 3 Front CTG GGC TAC ACT GAG CAC C 4 reverse AAG TGG TCG TTG AGG GCA ATG

[表3] 菌株名 相對TNF-α基因表現量 對照(PBS) 100.0±11.5 戊糖片球菌(Pediococcus pentosaceus)No.1菌株 91.6±20.7 嗜酸乳桿菌(Lactobacillus acidophilus)SBT2062菌株 45.2±2.6※ 瑞士乳桿菌(Lactobacillus helveticus)SBT2161菌株 32.1±2.3※ 瑞士乳桿菌(Lactobacillus helveticus)SBT2171菌株 40.4±1.2※ 唾液乳桿菌(Lactobacillus salivarius)SBT2687菌株 6.3±2.9※ 唾液乳桿菌(Lactobacillus salivarius)SBT2651菌株 10.4±9.9※ 唾液乳桿菌唾液亞種(Lactobacillus salivarius subsp. salivarius)SBT2670菌株 15.4±17.5※ 口腔鏈球菌(Streptococcus oralis)SBT0320菌株 25.5±1.2※ 乳酸乳球菌乳酸亞種(Lactococcus lactis subsp. lactis)SBT0625菌株 18.7±10.6※ 乳酸乳球菌乳脂亞種(Lactococcus lactis subsp. cremoris)SBT11373菌株 22.6±0.8※ 勞氏乳球菌(Lactococcus laudensis)SBT11178菌株 17.9±1.3※ 長雙歧桿菌(Bifidobacterium longum)SBT2928菌株 28.5±11.5※ 嗜熱雙歧桿菌(Bifidobacterium thermophilum)SBT2992菌株 21.7±0.6※ 數值係表示平均值±標準差(n=3) ※表示與對照(PBS)相比較具有顯著差異(p＜0.05) [table 3] strain name Relative TNF-α gene expression Control (PBS) 100.0±11.5 Pediococcus pentosaceus No.1 strain 91.6±20.7 Lactobacillus acidophilus SBT2062 strain 45.2±2.6※ Lactobacillus helveticus SBT2161 strain 32.1±2.3※ Lactobacillus helveticus SBT2171 strain 40.4±1.2※ Lactobacillus salivarius SBT2687 strain 6.3±2.9※ Lactobacillus salivarius SBT2651 strain 10.4±9.9※ Lactobacillus salivarius subsp. salivarius SBT2670 strain 15.4±17.5※ Streptococcus oralis SBT0320 strain 25.5±1.2※ Lactococcus lactis subsp. lactis SBT0625 strain 18.7±10.6※ Lactococcus lactis subsp. cremoris SBT11373 strain 22.6±0.8※ Lactococcus laudensis SBT11178 strain 17.9±1.3※ Bifidobacterium longum SBT2928 strain 28.5±11.5※ Bifidobacterium thermophilum SBT2992 strain 21.7±0.6※ Values represent mean ± standard deviation (n=3) ※Indicates a significant difference compared with the control (PBS) (p<0.05)

其結果，添加了嗜酸乳桿菌(Lactobacillus acidophilus)SBT2062菌株、瑞士乳桿菌(Lactobacillus helveticus)SBT2161菌株、SBT2171菌株、唾液乳桿菌(Lactobacillus salivarius)SBT2687菌株、SBT2651菌株、唾液乳桿菌唾液亞種(Lactobacillus salivarius subsp. salivarius)SBT2670菌株、口腔鏈球菌(Streptococcus oralis)SBT0320菌株、乳酸乳球菌乳酸亞種(Lactococcus lactis subsp. lactis)SBT0625菌株、乳酸乳球菌乳脂亞種(Lactococcus lactis subsp. cremoris)SBT11373菌株、勞氏乳球菌(Lactococcus laudensis)SBT11178菌株、長雙歧桿菌(Bifidobacterium longum)SBT2928菌株、嗜熱雙歧桿菌(Bifidobacterium thermophilum)SBT2992菌株之菌體破碎物時，與對照(PBS)相比較皆顯著地抑制滑膜細胞中之TNF-α基因的表現。因此，可知本發明之嗜酸乳桿菌(Lactobacillus acidophilus)SBT2062菌株、瑞士乳桿菌(Lactobacillus helveticus)SBT2161菌株、SBT2171菌株、唾液乳桿菌(Lactobacillus salivarius)SBT2687菌株、SBT2651菌株、唾液乳桿菌唾液亞種(Lactobacillus salivarius subsp. salivarius)SBT2670菌株、口腔鏈球菌(Streptococcus oralis)SBT0320菌株、乳酸乳球菌乳酸亞種(Lactococcus lactis subsp. lactis)SBT0625菌株、乳酸乳球菌乳脂亞種(Lactococcus lactis subsp. cremoris)SBT11373菌株、勞氏乳球菌(Lactococcus laudensis)SBT11178菌株、長雙歧桿菌(Bifidobacterium longum)SBT2928菌株、嗜熱雙歧桿菌(Bifidobacterium thermophilum)SBT2992菌株之菌體破碎物具有抑制滑膜細胞所致之發炎因子之產生的效果。另一方面，比較例品2之戊糖片球菌(Pediococcus pentosaceus)No.1菌株之菌體破碎物係未展現抑制滑膜細胞所致之發炎因子之產生的效果。As a result, Lactobacillus acidophilus SBT2062 strain, Lactobacillus helveticus SBT2161 strain, SBT2171 strain, Lactobacillus salivarius SBT2687 strain, SBT2651 strain, Lactobacillus helveticus subsp. salivarius subsp. salivarius) SBT2670 strain, Streptococcus oralis SBT0320 strain, Lactococcus lactis subsp. lactis SBT0625 strain, Lactococcus lactis subsp. cremoris SBT11373 strain, Lactococcus laudensis (Lactococcus laudensis) SBT11178 strain, Bifidobacterium longum (Bifidobacterium longum) SBT2928 strain, and Bifidobacterium thermophilum (Bifidobacterium thermophilum) SBT2992 strain's thallus fragments were significantly higher than those of the control (PBS). Inhibits expression of TNF-α gene in synoviocytes. Therefore, it can be known that Lactobacillus acidophilus (Lactobacillus acidophilus) SBT2062 bacterial strain of the present invention, Lactobacillus helveticus (Lactobacillus helveticus) SBT2161 bacterial strain, SBT2171 bacterial strain, Lactobacillus salivarius (Lactobacillus salivarius) SBT2687 bacterial strain, SBT2651 bacterial strain, Lactobacillus salivarius subsp. Lactobacillus salivarius subsp. salivarius) SBT2670 strain, Streptococcus oralis SBT0320 strain, Lactococcus lactis subsp. lactis SBT0625 strain, Lactococcus lactis subsp. cremoris SBT11373 strain , Lactococcus laudensis (Lactococcus laudensis) SBT11178 strain, Bifidobacterium longum (Bifidobacterium longum) SBT2928 strain, Bifidobacterium thermophilum (Bifidobacterium thermophilum) SBT2992 strain of the bacteria have the ability to inhibit the inflammatory factors caused by synoviocytes The effect produced. On the other hand, the crushed bacteria of Pediococcus pentosaceus No. 1 strain in Comparative Example 2 did not exhibit the effect of inhibiting the production of inflammatory factors caused by synoviocytes.

(試驗例3) 調查實施例品1之嗜酸乳桿菌(Lactobacillus acidophilus)SBT2062菌株、瑞士乳桿菌(Lactobacillus helveticus)SBT2161菌株、SBT2171菌株、唾液乳桿菌(Lactobacillus salivarius)SBT2687菌株、SBT2651菌株、唾液乳桿菌唾液亞種(Lactobacillus salivarius subsp. salivarius)SBT2670菌株、口腔鏈球菌(Streptococcus oralis)SBT0320菌株、實施例品2之乳酸乳球菌乳酸亞種(Lactococcus lactis subsp. lactis)SBT0625菌株、乳酸乳球菌乳脂亞種(Lactococcus lactis subsp. cremoris)SBT11373菌株、勞氏乳球菌(Lactococcus laudensis)SBT11178菌株、實施例品3之長雙歧桿菌(Bifidobacterium longum )SBT2928菌株、長雙歧桿菌嬰兒亞種(Bifidobacterium longum subsp. infantis)SBT2785菌株、假長雙歧桿菌(Bifidobacterium pseudolongum)SBT2922菌株之菌體破碎物之抑制滑膜細胞所為之軟骨基質分解因子之產生的效果。此外，為了比較，調查比較例品3之腸膜明串珠菌(Leuconostoc mesenteroides)No.1菌株之菌體破碎物之抑制滑膜細胞所為之軟骨基質分解因子之產生的效果。 將來自人類滑膜之細胞株(SW982)以成為100,000cells/well之方式接種至12孔之平板細胞培養盤，以含有10%(v/v)胎牛血清之Leibovitz’s L-15培養基於37℃、5%CO 2環境下培養1週。之後，去除全部的培養基，以不含胎牛血清之Leibovitz’s L-15培養基進行清洗並替換培養基。將human-IL-1β(Interleukin-1β)以最後濃度成為1ng/ml之方式添加至培養基，將本發明之菌體破碎物以最後濃度成為1mg/ml之方式添加至培養基，更培養24小時。之後，使用Sepasol RNA 1 SuperG 試藥(Nacalai Tesque Inc製)從培養後之細胞萃取全部的RNA。反轉錄反應係使用ReverTraAce qPCR RT Master Mix(東洋紡公司製)。使用獲得之cDNA，藉由THUNDERBIRD qPCR Mix(東洋紡公司製)進行即時PCR，定量為軟骨基質分解因子之MMP-13(Matrix Metalloproteinase-13)之基因表現量。此外，使用GAPDH(Glyceraldehyde-3-phosphate dehydrogenase)基因之表現量作為用以評價基因表現量的內部標準，分析中，對於MMP-13使用序列表序列編號5、6之引子，對於GAPDH使用序列表序列編號3、4之引子。 (Test Example 3) Investigation of Lactobacillus acidophilus (Lactobacillus acidophilus) SBT2062 strain, Lactobacillus helveticus (Lactobacillus helveticus) SBT2161 strain, SBT2171 strain, Lactobacillus salivarius (Lactobacillus salivarius) SBT2687 strain, SBT2651 strain, salivary milk Lactobacillus salivarius subsp. salivarius SBT2670 strain, Streptococcus oralis SBT0320 strain, Lactococcus lactis subsp. lactis SBT0625 strain of Example 2, Lactococcus lactis subsp. species (Lactococcus lactis subsp. cremoris) SBT11373 strain, Lactococcus laudensis (Lactococcus laudensis) SBT11178 strain, the Bifidobacterium longum (Bifidobacterium longum) SBT2928 strain of Example 3, Bifidobacterium longum subsp. Infantis) SBT2785 strain, Bifidobacterium pseudolongum (Bifidobacterium pseudolongum) SBT2922 strain's crushed bacteria inhibit the production of cartilage matrix decomposition factors produced by synoviocytes. In addition, for comparison, the effect of inhibiting the production of cartilage matrix decomposition factors produced by synoviocytes of the cell crushed product of Leuconostoc mesenteroides No. 1 strain of Comparative Example 3 was investigated. The cell line (SW982) from human synovium was inoculated into a 12-well plate cell culture dish at a rate of 100,000 cells/well, and cultured in Leibovitz's L-15 containing 10% (v/v) fetal bovine serum at 37°C , 5% CO 2 environment for 1 week. Thereafter, all the medium was removed, washed with Leibovitz's L-15 medium without fetal bovine serum, and the medium was replaced. Human-IL-1β (Interleukin-1β) was added to the medium at a final concentration of 1 ng/ml, and the disrupted bacterial cells of the present invention were added to the medium at a final concentration of 1 mg/ml, and cultured for 24 hours. Thereafter, all RNA was extracted from the cultured cells using Sepasol RNA 1 SuperG reagent (manufactured by Nacalai Tesque Inc). For the reverse transcription reaction, ReverTraAce qPCR RT Master Mix (manufactured by Toyobo Co., Ltd.) was used. Using the obtained cDNA, real-time PCR was performed with THUNDERBIRD qPCR Mix (manufactured by Toyobo Co., Ltd.), and the gene expression level of MMP-13 (Matrix Metalloproteinase-13), which is a cartilage matrix decomposition factor, was quantified. In addition, the expression level of the GAPDH (Glyceraldehyde-3-phosphate dehydrogenase) gene was used as an internal standard for evaluating the gene expression level. In the analysis, the primers of sequence numbers 5 and 6 in the sequence listing were used for MMP-13, and the sequence listing sequence numbers were used for GAPDH Primers of sequence numbers 3 and 4.

[表4] 序列編號   鹼基序列(5'=3') 5 前置 TCC TGA TGT GGG TGA ATA CAA TG 6 反置 GCC ATC GTG AAG TCT GGT AAA AT 3 前置 CTG GGC TAC ACT GAG CAC C 4 反置 AAG TGG TCG TTG AGG GCA ATG [Table 4] serial number Base sequence (5'=3') 5 Front TCC TGA TGT GGG TGA ATA CAA TG 6 reverse GCC ATC GTG AAG TCT GGT AAA AT 3 Front CTG GGC TAC ACT GAG CAC C 4 reverse AAG TGG TCG TTG AGG GCA ATG

[表5] 菌株名 相對MMP-13基因表現量 對照(PBS) 100.0±41.5 腸膜明串珠菌(Leuconostoc mesenteroides)No.1菌株 83.7±26.2 嗜酸乳桿菌(Lactobacillus acidophilus)SBT2062菌株 32.7±14.0※ 瑞士乳桿菌(Lactobacillus helveticus)SBT2161菌株 43.6±13.0※ 瑞士乳桿菌(Lactobacillus helveticus)SBT2171菌株 42.3±11.4※ 唾液乳桿菌(Lactobacillus salivarius)SBT2687菌株 11.0±2.6※ 唾液乳桿菌(Lactobacillus salivarius)SBT2651菌株 22.0±4.0※ 唾液乳桿菌唾液亞種(Lactobacillus salivarius subsp. salivarius)SBT2670菌株 15.1±14.1※ 口腔鏈球菌(Streptococcus oralis)SBT0320菌株 24.3±11.5※ 乳酸乳球菌乳酸亞種(Lactococcus lactis subsp. lactis)SBT0625菌株 40.6±13.9※ 乳酸乳球菌乳脂亞種(Lactococcus lactis subsp. cremoris)SBT11373菌株 24.3±5.6※ 勞氏乳球菌(Lactococcus laudensis)SBT11178菌株 13.8±3.9※ 長雙歧桿菌(Bifidobacterium longum)SBT2928菌株 30.6±8.9※ 長雙歧桿菌嬰兒亞種(Bifidobacterium longum subsp. infantis)SBT2785菌株 36.7±6.8※ 假長雙歧桿菌(Bifidobacterium pseudolongum)SBT2922菌株 22.7±15.2※ 數值係表示平均值±標準差(n=3) ※表示與對照(PBS)相比較具有顯著差異(p＜0.05) [table 5] strain name Relative MMP-13 gene expression Control (PBS) 100.0±41.5 Leuconostoc mesenteroides No.1 strain 83.7±26.2 Lactobacillus acidophilus SBT2062 strain 32.7±14.0※ Lactobacillus helveticus SBT2161 strain 43.6±13.0※ Lactobacillus helveticus SBT2171 strain 42.3±11.4※ Lactobacillus salivarius SBT2687 strain 11.0±2.6※ Lactobacillus salivarius SBT2651 strain 22.0±4.0※ Lactobacillus salivarius subsp. salivarius SBT2670 strain 15.1±14.1※ Streptococcus oralis SBT0320 strain 24.3±11.5※ Lactococcus lactis subsp. lactis SBT0625 strain 40.6±13.9※ Lactococcus lactis subsp. cremoris SBT11373 strain 24.3±5.6※ Lactococcus laudensis SBT11178 strain 13.8±3.9※ Bifidobacterium longum SBT2928 strain 30.6±8.9※ Bifidobacterium longum subsp. infantis SBT2785 strain 36.7±6.8※ Bifidobacterium pseudolongum SBT2922 strain 22.7±15.2※ Values represent mean ± standard deviation (n=3) ※Indicates a significant difference compared with the control (PBS) (p<0.05)

其結果，添加了嗜酸乳桿菌(Lactobacillus acidophilus)SBT2062菌株、瑞士乳桿菌(Lactobacillus helveticus)SBT2161菌株、SBT2171菌株、唾液乳桿菌(Lactobacillus salivarius)SBT2687菌株、SBT2651菌株、唾液乳桿菌唾液亞種(Lactobacillus salivarius subsp. salivarius)SBT2670菌株、口腔鏈球菌(Streptococcus oralis)SBT0320菌株、乳酸乳球菌乳酸亞種(Lactococcus lactis subsp. lactis)SBT0625菌株、乳酸乳球菌乳脂亞種(Lactococcus lactis subsp. cremoris)SBT11373菌株、勞氏乳球菌(Lactococcus laudensis)SBT11178菌株、長雙歧桿菌(Bifidobacterium longum)SBT2928菌株、長雙歧桿菌嬰兒亞種(Bifidobacterium longum subsp. infantis)SBT2785菌株、假長雙歧桿菌(Bifidobacterium pseudolongum)SBT2922菌株之菌體破碎物的情況，相較於對照(PBS)，皆顯著地抑制滑膜細胞中之MMP-13基因的表現。因此，可知本發明之嗜酸乳桿菌(Lactobacillus acidophilus)SBT2062菌株、瑞士乳桿菌(Lactobacillus helveticus)SBT2161菌株、SBT2171菌株、唾液乳桿菌(Lactobacillus salivarius)SBT2687菌株、SBT2651菌株、唾液乳桿菌唾液亞種(Lactobacillus salivarius subsp. salivarius)SBT2670菌株、口腔鏈球菌(Streptococcus oralis)SBT0320菌株、乳酸乳球菌乳酸亞種(Lactococcus lactis subsp. lactis)SBT0625菌株、乳酸乳球菌乳脂亞種(Lactococcus lactis subsp. cremoris)SBT11373菌株、勞氏乳球菌(Lactococcus laudensis)SBT11178菌株、長雙歧桿菌(Bifidobacterium longum )SBT2928菌株、長雙歧桿菌嬰兒亞種(Bifidobacterium longum subsp. infantis)SBT2785菌株、假長雙歧桿菌(Bifidobacterium pseudolongum)SBT2922菌株之菌體破碎物具有抑制滑膜細胞所致之軟骨基質分解因子的產生的效果。另一方面，比較例品3之腸膜明串珠菌(Leuconostoc mesenteroides)No.1菌株之菌體破碎物係未展現抑制滑膜細胞所致之軟骨基質分解因子之產生的效果。As a result, Lactobacillus acidophilus SBT2062 strain, Lactobacillus helveticus SBT2161 strain, SBT2171 strain, Lactobacillus salivarius SBT2687 strain, SBT2651 strain, Lactobacillus helveticus subsp. salivarius subsp. salivarius) SBT2670 strain, Streptococcus oralis SBT0320 strain, Lactococcus lactis subsp. lactis SBT0625 strain, Lactococcus lactis subsp. cremoris SBT11373 strain, Lactococcus laudensis SBT11178 strain, Bifidobacterium longum SBT2928 strain, Bifidobacterium longum subsp. infantis SBT2785 strain, Bifidobacterium pseudolongum SBT2922 strain Compared with the control (PBS), the disrupted bacterial cells significantly inhibited the expression of the MMP-13 gene in the synoviocytes. Therefore, it can be known that Lactobacillus acidophilus (Lactobacillus acidophilus) SBT2062 bacterial strain of the present invention, Lactobacillus helveticus (Lactobacillus helveticus) SBT2161 bacterial strain, SBT2171 bacterial strain, Lactobacillus salivarius (Lactobacillus salivarius) SBT2687 bacterial strain, SBT2651 bacterial strain, Lactobacillus salivarius subsp. Lactobacillus salivarius subsp. salivarius) SBT2670 strain, Streptococcus oralis SBT0320 strain, Lactococcus lactis subsp. lactis SBT0625 strain, Lactococcus lactis subsp. cremoris SBT11373 strain , Lactococcus laudensis SBT11178 strain, Bifidobacterium longum SBT2928 strain, Bifidobacterium longum subsp. infantis SBT2785 strain, Bifidobacterium pseudolongum SBT2922 The thallus crushed product of the strain has the effect of inhibiting the production of cartilage matrix decomposition factors caused by synoviocytes. On the other hand, the disrupted bacterial body of Leuconostoc mesenteroides No. 1 strain of Comparative Example 3 did not exhibit the effect of inhibiting the production of cartilage matrix decomposition factors by synoviocytes.

(試驗例4) 調查實施例品1之唾液乳桿菌(Lactobacillus salivarius)SBT2687菌株、實施例品3之長雙歧桿菌嬰兒亞種(Bifidobacterium longum subsp. infantis)SBT2785菌株、假長雙歧桿菌(Bifidobacterium pseudolongum)SBT2922菌株之菌體破碎物之抑制滑膜細胞所為之疼痛因子之產生的效果。此外，為了比較，調查比較例品1之融合魏斯氏菌(Weissella confusa)No.1菌株之菌體破碎物之抑制滑膜細胞所為之疼痛因子之產生的效果。 將來自人類滑膜之細胞株(SW982)以成為100,000cells/well之方式接種至 12孔之平板細胞培養盤，以含有10%(v/v)胎牛血清之Leibovitz’sL-15培養基於37℃、5%CO 2環境下培養1週。之後，去除全部的培養基，以不含胎牛血清之Leibovitz’s L-15培養基進行清洗並替換培養基。將human-IL-1β(Interleukin-1β)以最後濃度成為1ng/ml之方式添加至培養基，將本發明之菌體破碎物以最後濃度成為1mg/ml之方式添加至培養基，更培養24小時。之後，使用Sepasol RNA 1 SuperG 試藥(Nacalai Tesque Inc製)從培養後之細胞萃取全部的RNA。反轉錄反應係使用ReverTra Ace qPCR RT Master Mix(東洋紡公司製)。使用獲得之cDNA，藉由THUNDERBIRD qPCR Mix(東洋紡公司製)進行即時PCR，定量為疼痛因子之COX-2(Cyclooxygenase-2)之基因表現量。此外，使用GAPDH(Glyceraldehyde-3-phosphate dehydrogenase)基因之表現量作為用以評價基因表現量之內部標準，分析中，對於COX-2使用序列表序列編號7、8之引子，對於GAPDH使用序列表序列編號3、4之引子。 (Test Example 4) Investigate the Lactobacillus salivarius (Lactobacillus salivarius) SBT2687 strain of Example 1, the Bifidobacterium longum subsp. infantis SBT2785 strain of Example 3, Bifidobacterium pseudolongum Pseudolongum) SBT2922 bacterial cell fragments inhibit the production of pain factors produced by synoviocytes. In addition, for comparison, the effect of inhibiting the production of pain factors produced by synoviocytes of the disrupted bacterial cells of the fused Weissella confusa No. 1 strain of Comparative Example 1 was investigated. The cell line (SW982) from human synovium was inoculated into a 12-well plate cell culture plate in a manner of 100,000 cells/well, and cultured in Leibovitz'sL-15 containing 10% (v/v) fetal bovine serum on a 37 ℃, 5% CO 2 environment for 1 week. Thereafter, all the medium was removed, washed with Leibovitz's L-15 medium without fetal bovine serum, and the medium was replaced. Human-IL-1β (Interleukin-1β) was added to the medium at a final concentration of 1 ng/ml, and the disrupted bacterial cells of the present invention were added to the medium at a final concentration of 1 mg/ml, and cultured for 24 hours. Thereafter, all RNA was extracted from the cultured cells using Sepasol RNA 1 SuperG reagent (manufactured by Nacalai Tesque Inc). For the reverse transcription reaction, ReverTra Ace qPCR RT Master Mix (manufactured by Toyobo Co., Ltd.) was used. Using the obtained cDNA, real-time PCR was performed with THUNDERBIRD qPCR Mix (manufactured by Toyobo Co., Ltd.), and the gene expression level of COX-2 (Cyclooxygenase-2), which is a pain factor, was quantified. In addition, the expression of GAPDH (Glyceraldehyde-3-phosphate dehydrogenase) gene was used as an internal standard for evaluating gene expression. In the analysis, the primers of sequence number 7 and 8 were used for COX-2, and the sequence table for GAPDH was used Primers of sequence numbers 3 and 4.

[表6] 序列編號   鹼基序列(5'=3') 7 前置 ATG CTG ACT ATG GCT ACA AAA GC 8 反置 TCG GGC AAT CAT CAG GCA C 3 前置 CTG GGC TAC ACT GAG CAC C 4 反置 AAG TGG TCG TTG AGG GCA ATG [Table 6] serial number Base sequence (5'=3') 7 Front ATG CTG ACT ATG GCT ACA AAA GC 8 reverse TCG GGC AAT CAT CAG GCA C 3 Front CTG GGC TAC ACT GAG CAC C 4 reverse AAG TGG TCG TTG AGG GCA ATG

[表7] 菌株名 相對COX-2基因表現量 對照(PBS) 100.0±20.0※ 融合魏斯氏菌(Weissella confusa)No.1菌株 118.0±31.8※ 唾液乳桿菌(Lactobacillus salivarius)SBT2687菌株 28.6±24.0※ 長雙歧桿菌嬰兒亞種(Bifidobacterium longum subsp. infantis)SBT2785菌株 35.7±15.8※ 假長雙歧桿菌(Bifidobacterium pseudolongum)SBT2922菌株 48.7±9.3※ 數值係表示平均值±標準差(n=3) ※表示與對照(PBS)相比較具有顯著差異(p＜0.05) [Table 7] strain name Relative COX-2 gene expression Control (PBS) 100.0±20.0※ Fusion Weissella confusa No.1 strain 118.0±31.8※ Lactobacillus salivarius SBT2687 strain 28.6±24.0※ Bifidobacterium longum subsp. infantis SBT2785 strain 35.7±15.8※ Bifidobacterium pseudolongum SBT2922 strain 48.7±9.3※ Values represent mean ± standard deviation (n=3) ※Indicates a significant difference compared with the control (PBS) (p<0.05)

其結果，添加了唾液乳桿菌(Lactobacillus salivarius)SBT2687菌株、長雙歧桿菌嬰兒亞種(Bifidobacterium longum subsp. infantis)SBT2785菌株、假長雙歧桿菌(Bifidobacterium pseudolongum)SBT2922菌株之菌體破碎物時，相較於對照(PBS)，皆顯著地抑制滑膜細胞中之COX-2基因的表現。因此，可知本發明之唾液乳桿菌(Lactobacillus salivarius)SBT2687菌株、長雙歧桿菌嬰兒亞種(Bifidobacterium longum subsp. infantis)SBT2785菌株、假長雙歧桿菌(Bifidobacterium pseudolongum)SBT2922菌株之菌體破碎物，具有抑制滑膜細胞所致之疼痛因子之產生的效果。另一方面，比較例品1之融合魏斯氏菌(Weissella confusa)No.1菌株之菌體破碎物係未展現抑制滑膜細胞所致之疼痛因子之產生的效果。As a result, when Lactobacillus salivarius SBT2687 strain, Bifidobacterium longum subsp. infantis SBT2785 strain, and Bifidobacterium pseudolongum SBT2922 strain were added, Compared with the control (PBS), all significantly inhibited the expression of COX-2 gene in synoviocytes. Therefore, it can be known that Lactobacillus salivarius (Lactobacillus salivarius) SBT2687 bacterial strain of the present invention, Bifidobacterium longum subsp. It has the effect of inhibiting the production of pain factors caused by synoviocytes. On the other hand, the disrupted cell line of Comparative Example 1 fused with Weissella confusa No. 1 strain did not exhibit the effect of inhibiting the production of pain factors induced by synoviocytes.

(試驗例5) 調查實施例品1之唾液乳桿菌(Lactobacillus salivarius)SBT2687菌株、SBT2651菌株、實施例品3之長雙歧桿菌嬰兒亞種(Bifidobacterium longum subsp. infantis)SBT2785菌株、假長雙歧桿菌(Bifidobacterium pseudolongum)SBT2922菌株之菌體破碎物之抑制滑膜細胞所為之神經伸長因子之產生的效果。此外，為了比較，調查比較例品2之戊糖片球菌(Pediococcus pentosaceus)No.1菌株之菌體破碎物的抑制滑膜細胞所為之神經伸長因子之產生的效果。 將來自人類滑膜之細胞株(SW982)以成為100,000cells/well之方式接種至 12孔之平板細胞培養盤，以含有10%(v/v)胎牛血清之Leibovitz’s L-15培養基於37℃、5%CO 2環境下培養1週。之後，去除全部的培養基，以不含胎牛血清之Leibovitz’s L-15培養基進行清洗並替換培養基。將human-IL-1β(Interleukin-1β)以最後濃度成為1ng/ml之方式添加至培養基，將本發明之菌體破碎物以最後濃度成為1mg/ml之方式添加至培養基，更培養24小時。之後，使用Sepasol RNA 1 SuperG 試藥(Nacalai Tesque Inc製)從培養後之細胞萃取全部的RNA。反轉錄反應係使用ReverTra Ace qPCR RT Master Mix(東洋紡公司製)。使用獲得之cDNA，藉由THUNDERBIRD qPCR Mix(東洋紡公司製)進行即時PCR，定量為神經伸長因子之NGF(Nerve Growth Factor)之基因的表現量。此外，使用GAPDH(Glyceraldehyde-3-phosphate dehydrogenase)基因之表現量作為用以評價基因表現量之內部標準，分析中，對於NGF使用序列表序列編號9、10之引子，對於GAPDH使用序列表序列編號3、4之引子。 (Test Example 5) Investigate the Lactobacillus salivarius (Lactobacillus salivarius) SBT2687 strain, SBT2651 strain of Example 1, the Bifidobacterium longum subsp. infantis (Bifidobacterium longum subsp. Bacillus (Bifidobacterium pseudolongum) SBT2922 bacterial cell fragments inhibit synovial cell nerve elongation factor production effect. In addition, for comparison, the effect of inhibiting the production of nerve elongation factor produced by synoviocytes of the crushed bacteria of Pediococcus pentosaceus (Pediococcus pentosaceus) No. 1 strain of Comparative Example 2 was investigated. The cell line (SW982) from human synovium was inoculated into a 12-well plate cell culture dish at a rate of 100,000 cells/well, and cultured in Leibovitz's L-15 containing 10% (v/v) fetal bovine serum at 37°C , 5% CO 2 environment for 1 week. Thereafter, all the medium was removed, washed with Leibovitz's L-15 medium without fetal bovine serum, and the medium was replaced. Human-IL-1β (Interleukin-1β) was added to the medium at a final concentration of 1 ng/ml, and the disrupted bacterial cells of the present invention were added to the medium at a final concentration of 1 mg/ml, and cultured for 24 hours. Thereafter, all RNA was extracted from the cultured cells using Sepasol RNA 1 SuperG reagent (manufactured by Nacalai Tesque Inc). For the reverse transcription reaction, ReverTra Ace qPCR RT Master Mix (manufactured by Toyobo Co., Ltd.) was used. Using the obtained cDNA, real-time PCR was performed with THUNDERBIRD qPCR Mix (manufactured by Toyobo Co., Ltd.) to quantify the expression level of the NGF (Nerve Growth Factor) gene which is a nerve elongation factor. In addition, the expression of GAPDH (Glyceraldehyde-3-phosphate dehydrogenase) gene is used as an internal standard for evaluating gene expression. In the analysis, the primers of sequence number 9 and 10 are used for NGF, and the sequence number of GAPDH is used 3. Introduction to 4.

[表8] 序列編號   鹼基序列(5'=3') 9 前置 GGC AGA CCC GCA ACA TTA CT 10 反置 CAC CAC CGA CCT CGA AGT C 3 前置 CTG GGC TAC ACT GAG CAC C 4 反置 AAG TGG TCG TTG AGG GCA ATG [Table 8] serial number Base sequence (5'=3') 9 Front GGC AGA CCC GCA ACA TTA CT 10 reverse CAC CAC CGA CCT CGA AGT C 3 Front CTG GGC TAC ACT GAG CAC C 4 reverse AAG TGG TCG TTG AGG GCA ATG

[表9] 菌株名 相對NGF基因表現量 對照(PBS) 100.0±13.4※ 戊糖片球菌(Pediococcus pentosaceus)No.1菌株 94.3±24.1※ 唾液乳桿菌(Lactobacillus salivarius)SBT2687菌株 23.6±3.4※ 唾液乳桿菌(Lactobacillus salivarius)SBT2651菌株 38.1±10.2※ 長雙歧桿菌嬰兒亞種(Bifidobacterium longum subsp. infantis)SBT2785菌株 17.8±4.6※ 假長雙歧桿菌(Bifidobacterium pseudolongum)SBT2922菌株 44.8±12.7※ 數值係表示平均值±標準差(n=3) ※表示與對照(PBS)相比較具有顯著差異(p＜0.05) [Table 9] strain name relative NGF gene expression Control (PBS) 100.0±13.4※ Pediococcus pentosaceus No.1 strain 94.3±24.1※ Lactobacillus salivarius SBT2687 strain 23.6±3.4※ Lactobacillus salivarius SBT2651 strain 38.1±10.2※ Bifidobacterium longum subsp. infantis SBT2785 strain 17.8±4.6※ Bifidobacterium pseudolongum SBT2922 strain 44.8±12.7※ Values represent mean ± standard deviation (n=3) ※Indicates a significant difference compared with the control (PBS) (p<0.05)

其結果，添加了唾液乳桿菌(Lactobacillus salivarius)SBT2687菌株、SBT2651菌株、長雙歧桿菌嬰兒亞種(Bifidobacterium longum subsp. infantis)SBT2785菌株、假長雙歧桿菌(Bifidobacterium pseudolongum)SBT2922菌株之菌體破碎物的情況，相較於對照(PBS)，皆顯著地抑制了滑膜細胞中之NGF基因的表現。因此，可知本發明之唾液乳桿菌(Lactobacillus salivarius)SBT2687菌株、SBT2651菌株、長雙歧桿菌嬰兒亞種(Bifidobacterium longum subsp. infantis)SBT2785菌株、假長雙歧桿菌(Bifidobacterium pseudolongum)SBT2922菌株之菌體破碎物，具有抑制滑膜細胞所致之神經伸長因子之產生的效果。另一方面，比較例品2之戊糖片球菌(Pediococcus pentosaceus)No.1菌株之菌體破碎物，係未展現抑制滑膜細胞所致之神經伸長因子之產生的效果。As a result, Lactobacillus salivarius SBT2687 strain, SBT2651 strain, Bifidobacterium longum subsp. infantis SBT2785 strain, and Bifidobacterium pseudolongum SBT2922 strain were added to disrupt the bacterial cells. Compared with the control (PBS), the expression of NGF gene in synoviocytes was significantly suppressed. Therefore, it can be known that the bacterial cells of Lactobacillus salivarius SBT2687 bacterial strain, SBT2651 bacterial strain, Bifidobacterium longum subsp. infantis SBT2785 bacterial strain, Bifidobacterium pseudolongum SBT2922 bacterial strain of the present invention Crushed matter has the effect of inhibiting the production of nerve elongation factor induced by synoviocytes. On the other hand, the crushed bacteria of Pediococcus pentosaceus No. 1 strain of Comparative Example 2 did not exhibit the effect of inhibiting the production of nerve elongation factor by synoviocytes.

(實施例4) (關節功能改善用膠囊劑之調製) 按表10所示之摻合混合原材料後，藉由通常方法進行造粒，填充至膠囊，而製造本發明之關節功能改善用膠囊劑。 (Example 4) (Preparation of capsules for improving joint function) After blending and mixing the raw materials as shown in Table 10, granulate them by the usual method, and fill them into capsules to manufacture the capsules for improving joint function of the present invention.

[表10] 重量(%) SBT2062菌株(實施例品1) 0.1 乳糖 41.4 可溶性澱粉 58.0 硬脂酸鎂 0.5 [Table 10] weight(%) SBT2062 bacterial strain (embodiment product 1) 0.1 lactose 41.4 soluble starch 58.0 Magnesium stearate 0.5

(實施例5) (關節功能改善用錠劑之調製) 按表11所示之摻合混合原材料後，藉由通常方法成型並打錠為1g來製造本發明之關節功能改善用錠劑。 (Example 5) (Preparation of lozenges for joint function improvement) After blending and mixing raw materials as shown in Table 11, the tablet for improving joint function of the present invention was manufactured by molding and tableting into 1 g by a usual method.

[表11] 重量(%) 含水結晶葡萄糖 93.49 SBT2161菌株(實施例品1) 0.01 礦物質混合 5.00 糖酯 1.00 香料 0.50 [Table 11] weight(%) hydrated crystalline glucose 93.49 SBT2161 strain (Example 1) 0.01 mineral blend 5.00 sugar ester 1.00 spices 0.50

(實施例6) (關節功能改善用液狀營養組成物之調製) 將SBT2171株之菌體(實施例品1)25g溶解於4975g之去離子水中，加熱至40℃後，藉由TK均質混合機(TK ROBO MICS；特殊機化工業公司製)，以6,000rpm攪拌10分鐘予以混合，獲得25g/5kg之SBT2171菌株之菌體溶液。對於該SBT2171菌株溶液5.0kg，摻合酪蛋白5.0kg、大豆蛋白質5.0kg、魚油1.0kg、紫蘇油3.0kg、糊精17.0kg、礦物質混合物6.0kg、維生素混合物1.95kg、乳化劑2.0kg、安定劑4.0kg、香料0.05kg，填充至200ml之蒸煮袋(retort pouch)，以蒸煮殺菌機(第一種壓力容器、TYPE： RCS-4CRTGN、日阪製作所製)進行121℃、20分鐘之殺菌，製造本發明之關節功能改善用液狀營養組成物50kg。此外，本發明之關節功能改善用液狀營養組成物200g中，含有SBT2171菌株之菌體100mg。 (Example 6) (Preparation of liquid nutrient composition for joint function improvement) Dissolve 25 g of the bacteria of SBT2171 strain (Example 1) in 4975 g of deionized water, heat to 40°C, and stir at 6,000 rpm with a TK homomixer (TK ROBO MICS; made by Tokuki Kagaku Kogyo Co., Ltd.) Mix for 10 minutes to obtain 25 g/5 kg of the bacterial cell solution of the SBT2171 strain. For 5.0 kg of the SBT2171 strain solution, 5.0 kg of casein, 5.0 kg of soybean protein, 1.0 kg of fish oil, 3.0 kg of perilla oil, 17.0 kg of dextrin, 6.0 kg of mineral mixture, 1.95 kg of vitamin mixture, 2.0 kg of emulsifier, 4.0kg of stabilizer, 0.05kg of fragrance, filled to 200ml retort pouch, and sterilized at 121°C for 20 minutes with a retort sterilizer (first pressure vessel, TYPE: RCS-4CRTGN, manufactured by Hisaka Seisakusho) , Manufacture 50 kg of the liquid nutritional composition for improving joint function of the present invention. In addition, 200 g of the liquid nutrient composition for improving joint function of the present invention contains 100 mg of bacterial cells of the SBT2171 strain.

(實施例7) (關節功能改善用飲料之調製) 將實施例品1之SBT2687菌株之菌體0.5g溶解於699.5g之去離子水後，加熱至40℃後，藉由超分散器(ULTRA-TURRAX T-25；Ika Japan K.K.製)，以9,500rpm攪拌20分鐘混合。添加麥芽糖醇100g、酸味劑2g、還原水20g、香料2g、去離子水176g後，填充至100ml之玻璃瓶，經95℃、15秒鐘殺菌後，密封，製備本發明之關節功能改善用飲料10瓶(100ml裝)。此外，本發明之關節功能改善用飲料100g中，含有SBT2687菌株之菌體50mg。 (Example 7) (The preparation of beverages for improving joint function) Dissolve 0.5 g of the SBT2687 strain of Example 1 in 699.5 g of deionized water, heat it to 40°C, and use an ultra-disperser (ULTRA-TURRAX T-25; manufactured by Ika Japan K.K.) at 9,500 Mix at rpm for 20 minutes. After adding 100g of maltitol, 2g of sour agent, 20g of reduced water, 2g of spices, and 176g of deionized water, fill it into a 100ml glass bottle, sterilize it at 95°C for 15 seconds, and seal it to prepare the beverage for improving joint function of the present invention. 10 bottles (100ml). Furthermore, 100 g of the beverage for improving joint function of the present invention contains 50 mg of bacterial cells of the SBT2687 strain.

(實施例8) (犬用關節功能改善用飼料之調製) 將實施例品1之SBT2651菌株之菌體2g溶解於3,998g之去離子水中，加熱至40℃後，藉由TK均質混合機(MARK II 160型；特殊機化工業公司製)，以3,600rpm攪拌20分鐘予以混合，獲得2g/4kg之SBT2651菌株之菌體溶液。對於該SBT2651菌株之菌體溶液2kg摻合大豆粕1kg、脫脂奶粉1kg、大豆油0.4kg、玉米油0.2kg、棕櫚油2.3kg、玉米澱粉1kg、小麥粉0.9kg、麩0.2kg、維生素混合物0.5kg、纖維素0.3kg、礦物質混合物0.2kg，進行120℃、4分鐘的加熱殺菌，製造本發明之關節功能改善用飼料10kg。此外，本發明之關節功能改善用飼料100g中含有SBT2651菌株之菌體10mg。 (Embodiment 8) (Preparation of feed for improving joint function of dogs) Dissolve 2 g of the SBT2651 strain of Example 1 in 3,998 g of deionized water, heat it to 40°C, and heat it at 3,600 rpm with a TK homomixer (MARK II 160; made by Tokuki Kagaku Kogyo Co., Ltd.). Stir for 20 minutes to mix, and obtain a 2 g/4 kg bacterial cell solution of SBT2651 strain. For 2 kg of the bacterial cell solution of the SBT2651 strain, 1 kg of soybean meal, 1 kg of skimmed milk powder, 0.4 kg of soybean oil, 0.2 kg of corn oil, 2.3 kg of palm oil, 1 kg of corn starch, 0.9 kg of wheat flour, 0.2 kg of bran, and 0.5 kg of vitamin mixture kg, 0.3 kg of cellulose, and 0.2 kg of mineral mixture were heat-sterilized at 120° C. for 4 minutes to prepare 10 kg of the joint function-improving feed of the present invention. In addition, 100 g of the feed for improving joint function of the present invention contains 10 mg of bacterial cells of the SBT2651 strain.

(實施例9) (關節功能改善用奶粉的調製) 將實施例品1之SBT2670菌株的菌體2g、脫脂奶粉9.998kg、去離子水90kg混合，加熱至40℃後，藉由TK均質混合機(TK ROBO MICS；特殊機化工業公司製)，以6,000rpm攪拌混合10分鐘。將該溶液進行噴霧乾燥來製造本發明之關節功能改善用奶粉10kg。此外，本發明之關節功能改善用奶粉10g中含有SBT2670菌株之菌體2mg。 (Example 9) (The preparation of milk powder for improving joint function) Mix 2 g of the SBT2670 bacterial strain of Example 1, 9.998 kg of skimmed milk powder, and 90 kg of deionized water, heat to 40° C., and use a TK homomixer (TK ROBO MICS; manufactured by Tokuki Kagaku Kogyo Co., Ltd.) to Stir and mix at 6,000 rpm for 10 minutes. This solution was spray-dried to manufacture 10 kg of milk powder for improving joint function of the present invention. In addition, 10 g of milk powder for improving joint function of the present invention contains 2 mg of bacteria cells of the SBT2670 strain.

(實施例10) (關節功能改善用乳飲料之調製) 將實施例品2之SBT0625菌株之菌體1g、牛乳9.999kg混合，加熱至40℃後，藉由TK均質混合機(TK ROBO MICS；特殊機化工業公司製)，以6,000rpm攪拌混合10分鐘。以130℃經2秒鐘加熱殺菌後，冷卻至10℃以下，製造本發明之關節功能改善用乳飲料10kg。此外，本發明之關節功能改善用乳飲料200g中含有SBT0625菌株之菌體20mg。 (Example 10) (The preparation of milk drink for improving joint function) Mix 1 g of the SBT0625 bacterial strain of Example 2 and 9.999 kg of milk, heat to 40°C, and stir and mix at 6,000 rpm for 10 minutes with a TK homomixer (TK ROBO MICS; manufactured by Tokuki Kagaku Kogyo Co., Ltd.) . After heat sterilization at 130° C. for 2 seconds, cool to below 10° C. to manufacture 10 kg of the milk drink for improving joint function of the present invention. In addition, 200 g of the milk drink for improving joint function of the present invention contains 20 mg of bacteria cells of the SBT0625 strain.

(實施例11) (關節功能改善用發酵乳之調製) 混合實施例品2之SBT11373菌株之菌體0.1g、脫脂奶粉1700g、葡萄糖300g、去離子水7699.9g，於95℃維持2小時進行加熱殺菌。將其冷卻至37℃，接菌乳酸菌菌元(嗜熱鏈球菌(Streptococcus thermophilus))300g，攪拌混合後，使其在維持於37℃之培養箱內發酵直到成為pH4.0。到達pH4.0後冷卻至10℃以下，製造本發明之關節功能改善用發酵乳10kg。此外，本發明之關節功能改善用發酵乳200g中含有SBT11373菌株之菌體2mg。 (Example 11) (The preparation of fermented milk for joint function improvement) Mix 0.1 g of the SBT11373 bacterial strain of Example 2, 1,700 g of skim milk powder, 300 g of glucose, and 7,699.9 g of deionized water, and heat-sterilize it at 95° C. for 2 hours. It was cooled to 37° C., inoculated with 300 g of lactic acid bacteria (Streptococcus thermophilus), stirred and mixed, and fermented in an incubator maintained at 37° C. until pH 4.0. After reaching pH 4.0, it was cooled to below 10° C., and 10 kg of fermented milk for improving joint function of the present invention was produced. In addition, 200 g of fermented milk for improving joint function of the present invention contains 2 mg of bacterial cells of the SBT11373 strain.

(實施例12) (關節功能改善用乳酸菌飲料之調製) 混合脫脂奶粉1700g、葡萄糖300g、去離子水7700g，於95℃維持2小時進行加熱殺菌。將其冷卻至37℃，接菌乳酸菌菌元(乾酪乳桿菌(Lb. casei))300g，攪拌混合後，在維持於37℃之培養箱內發酵直到成為pH4.0。到達pH4.0後，邊攪拌邊冷卻至10℃以下，獲得發酵基質。此外，混合實施例品2之SBT11178菌株之菌體4g、上白糖1800g、酸味劑20g、香料10g、去離子水8166g，以90℃殺菌10分鐘後冷卻至10℃以下，獲得糖液。將上述發酵基質2000g與糖液8000g混合，藉由均質機使組織滑潤，分裝至200ml裝之50個紙容器中後，以鋁蓋密封，製造本發明之關節功能改善用乳酸菌飲料10kg。此外，本發明之關節功能改善用乳酸菌飲料200ml中，含有SBT11178菌株之菌體64mg。 (Example 12) (The preparation of lactic acid bacteria drink for improving joint function) Mix 1,700 g of skim milk powder, 300 g of glucose, and 7,700 g of deionized water, and maintain at 95° C. for 2 hours for heat sterilization. It was cooled to 37° C., inoculated with 300 g of lactic acid bacteria (Lactobacillus casei (Lb. casei)), stirred and mixed, and fermented in an incubator maintained at 37° C. until pH 4.0. After reaching pH 4.0, it was cooled to below 10°C while stirring to obtain a fermentation substrate. In addition, mix 4 g of SBT11178 bacterial strain of Example 2, 1,800 g of sugar, 20 g of sour agent, 10 g of flavor, and 8,166 g of deionized water, sterilize at 90°C for 10 minutes, and then cool to below 10°C to obtain a sugar solution. Mix 2000g of the above-mentioned fermentation substrate with 8000g of sugar solution, smooth the tissue with a homogenizer, divide it into 50 200ml paper containers, and seal it with an aluminum lid to manufacture 10kg of the lactic acid bacteria beverage for improving joint function of the present invention. In addition, 200 ml of the lactic acid bacteria beverage for improving joint function of the present invention contains 64 mg of bacterial cells of the SBT11178 strain.

(實施例13) (關節功能改善用軟飲料之調製) 將實施例品1之SBT0320菌株之菌體3g、50%乳酸0.75kg、赤蘚醇5.7kg、香料1kg、去離子水42.547kg混合，加熱至40℃後，藉由TK均質混合機(TK ROBO MICS；特殊機化工業公司製)，以6,000rpm攪拌10分鐘進行混合。將該溶液以90℃殺菌10分鐘後，冷卻至10℃以下，而製造本發明之關節功能改善用軟飲料50kg。此外，本發明之關節功能改善用軟飲料200ml中，含有SBT0320菌株之菌體12mg。 (Example 13) (Modulation of soft drinks for joint function improvement) Mix 3 g of the SBT0320 bacterial strain of Example 1, 0.75 kg of 50% lactic acid, 5.7 kg of erythritol, 1 kg of fragrance, and 42.547 kg of deionized water. MICS; manufactured by Tokuji Kikka Kogyo Co., Ltd.) was stirred and mixed at 6,000 rpm for 10 minutes. This solution was sterilized at 90° C. for 10 minutes, and then cooled to below 10° C. to manufacture 50 kg of the joint function-improving soft drink of the present invention. In addition, 200 ml of the soft drink for improving joint function of the present invention contains 12 mg of bacterial cells of the SBT0320 strain.

(實施例14) (關節功能改善用起司之調製) 混合哥達起司9.5kg、切達起司9.5kg、實施例品3之SBT2928菌株之菌體4g、檸檬酸鈉200g、去離子水796g，以85℃予以乳化。在乳化後將起司填充至紙盒(carton)以2晝夜、5℃予以冷卻，製造本發明之關節功能改善用起司20kg。此外，本發明之關節功能改善用起司100g中，含有SBT2928菌株之菌體20mg。 (Example 14) (Modulation of cheese for joint function improvement) Mix 9.5 kg of Gotha cheese, 9.5 kg of cheddar cheese, 4 g of bacteria cells of the SBT2928 strain of Example 3, 200 g of sodium citrate, and 796 g of deionized water, and emulsify at 85°C. After emulsification, the cheese was filled into a carton and cooled at 5° C. for 2 days and nights to manufacture 20 kg of the joint function-improving cheese of the present invention. In addition, 100 g of the cheese for improving joint function of the present invention contains 20 mg of bacteria cells of the SBT2928 strain.

(實施例15) (關節功能改善用人造奶油之調製) 混合大豆氫化油2kg、大豆白絞油4kg、棕櫚油2.5kg、脂肪酸甘油酯50g調製油層。然後，混合實施例品3之SBT2785菌株之菌體20g、乳酸10g、去離子水1420g，添加至油層獲得油中水型乳化物、將該乳化物以人造奶油製造機進行冷卻、固化及壓練，製造本發明之關節功能改善用人造奶油10kg。此外，本發明之關節功能改善用人造奶油10g中，含有SBT2785菌株之菌體20mg。 (Example 15) (modulation of margarine for joint function improvement) Mix 2 kg of soybean hydrogenated oil, 4 kg of soybean white twist oil, 2.5 kg of palm oil, and 50 g of fatty acid glycerides to prepare the oil layer. Then, mix 20 g of the SBT2785 bacterial strain of Example 3, 10 g of lactic acid, and 1420 g of deionized water, add to the oil layer to obtain a water-in-oil emulsion, and cool, solidify, and compress the emulsion with a margarine maker 10 kg of margarine for improving joint function of the present invention was manufactured. In addition, 10 g of margarine for improving joint function of the present invention contains 20 mg of bacterial cells of the SBT2785 strain.

(實施例16) (關節功能改善用乳油之調製) 混合菜籽氫化油4.5kg、卵磷脂40g、脂肪酸單甘油酯10g、山梨醇酐脂肪酸酯10g，調製油相。然後，混合實施例品3之SBT2922菌株之菌體40g、脫脂奶粉400g、酪蛋白鈉10g、糖酯20g、磷酸鹽10g、黃原膠5g、去離子水4.955kg，調製水相。將水相加熱至65℃，將已加熱至70℃之油相邊逐次少量地添加邊攪拌，藉由TK均質混合機(TK ROBO MICS；特殊機化工業公司製)，以6,000rpm攪拌10分鐘混合。將其以均質機進行均質處理製造本發明之關節功能改善用乳油10kg。此外，本發明之關節功能改善用乳油10g中，含有SBT2922菌株之菌體40mg。 (Example 16) (modulation of emulsifiable oil for joint function improvement) Mix 4.5kg of rapeseed hydrogenated oil, 40g of lecithin, 10g of fatty acid monoglyceride, and 10g of sorbitan fatty acid ester to prepare an oil phase. Then, mix 40 g of the bacterial cells of SBT2922 strain of Example 3, 400 g of skimmed milk powder, 10 g of sodium caseinate, 20 g of sugar ester, 10 g of phosphate, 5 g of xanthan gum, and 4.955 kg of deionized water to prepare an aqueous phase. Heat the water phase to 65°C, add the oil phase heated to 70°C little by little while stirring, and stir at 6,000rpm for 10 minutes with a TK homomixer (TK ROBO MICS; made by Tokuki Kagaku Kogyo Co., Ltd.) mix. Carry out homogenization treatment with a homogenizer to manufacture emulsifiable concentrate 10kg for joint function improvement of the present invention. In addition, 10 g of the emulsifiable concentrate for improving joint function of the present invention contains 40 mg of bacterial cells of the SBT2922 strain.

(實施例17) (關節功能改善用布丁之調製) 混合蜂蜜2000g、實施例品3之SBT2992菌株之菌體4g、脫脂奶粉800g、馬斯卡彭起司(mascarpone)300g、液狀水700g、晶粒砂糖500g、鮮奶油250g、奶油200g、加糖蛋黃400g、明膠40g、洋菜膠15g、刺槐豆膠120g、去離子水4671g，製成布丁混合物。將該布丁混合物藉由TK均質混合機(TK ROBO MICS；特殊機化工業公司製)，以6,000rpm攪拌10分鐘予以混合，加熱至60℃溶解後，每100g填充至容器並冷卻，藉此製造本發明之關節功能改善用布丁100個。此外，本發明之關節功能改善用布丁100g中，含有SBT2992菌株之菌體40mg。 (Example 17) (The preparation of pudding for joint function improvement) Mix 2000g of honey, 4g of SBT2992 bacterial strain of Example 3, 800g of skimmed milk powder, 300g of mascarpone cheese (mascarpone), 700g of liquid water, 500g of crystal sugar, 250g of fresh cream, 200g of cream, and sugared egg yolk 400g, 40g gelatin, 15g agaric gum, 120g locust bean gum, 4671g deionized water to make a pudding mixture. This pudding mixture was mixed with a TK homomixer (TK ROBO MICS; manufactured by Tokukuki Kagaku Kogyo Co., Ltd.) at 6,000 rpm for 10 minutes, heated to 60°C and dissolved, filled into a container per 100 g and cooled to produce 100 puddings for improving joint function of the present invention. In addition, 100 g of the pudding for improving joint function of the present invention contains 40 mg of bacterial cells of the SBT2992 strain.

(實施例18) (關節功能改善用果凍之調製) 混合實施例品1之SBT2687菌株之菌體4.4g、果糖2000g、晶粒砂糖1500g、水500g、洋菜膠100g、香料10g、去離子水5885.6g，藉由TK均質混合機(TK ROBO MICS；特殊機化工業公司製)，以6,000rpm攪拌10分鐘予以混合，加熱至50℃溶解後，每100g填充至容器並冷卻，藉此製造本發明之關節功能改善用果凍100個。此外，本發明之關節功能改善用果凍100g中，含有SBT2687菌株之菌體44mg。 (Example 18) (modulation of jelly for improving joint function) Mix 4.4g of the SBT2687 bacterial strain of Example 1, 2000g of fructose, 1500g of granulated sugar, 500g of water, 100g of agaric gum, 10g of spices, and 5885.6g of deionized water, with a TK homomixer (TK ROBO MICS; Tokuki Kagaku Kogyo Co., Ltd.), mixed at 6,000 rpm for 10 minutes, heated to 50°C to dissolve, filled into a container per 100 g and cooled, thereby manufacturing 100 pieces of jelly for improving joint function of the present invention. In addition, 100 g of the jelly for improving joint function of the present invention contains 44 mg of bacterial cells of the SBT2687 strain.

(實施例19) (關節功能改善用威化餅之調製) 混合實施例品1之SBT2651菌株之菌體9.2g、小麥粉8.5kg、玉米澱粉1.21kg、棕櫚油0.22kg、膨脹劑0.05kg後，添加適量的去離子水調製麵糊後，藉由威化餅烘焙機進行烘焙，製造本發明之關節功能改善用威化餅10kg。此外，本發明之關節功能改善用威化餅50g中含有SBT2651菌株之菌體46mg。 [產業上利用性] (Example 19) (The preparation of wafers for improving joint function) After mixing 9.2g of the SBT2651 bacterial strain of Example 1, 8.5kg of wheat flour, 1.21kg of cornstarch, 0.22kg of palm oil, and 0.05kg of expansion agent, after adding an appropriate amount of deionized water to prepare the batter, the wafer Baking was carried out in a baking machine to manufacture 10 kg of wafers for improving joint function of the present invention. In addition, 50 g of wafers for improving joint function of the present invention contained 46 mg of bacterial cells of the SBT2651 strain. [industrial availability]

根據本發明可提供能長期攝取、且安全性高，藉由促進軟骨細胞之增殖的作用、或抑制滑膜細胞所致之發炎因子、軟骨基質分解因子、疼痛因子、神經伸長因子之產生的作用而得之關節功能改善作用明顯的關節功能改善用組成物。因此，藉由攝取本發明能夠預防或治療以退化性膝關節炎為代表之退化性關節炎或類風濕性關節炎等之各種關節疾病。According to the present invention, it can be taken for a long time and has high safety, by promoting the proliferation of chondrocytes, or inhibiting the production of inflammatory factors, cartilage matrix decomposition factors, pain factors, and nerve elongation factors caused by synoviocytes. The obtained composition for improving joint function has a significant effect of improving joint function. Therefore, various joint diseases such as osteoarthritis represented by osteoarthritis or rheumatoid arthritis can be prevented or treated by ingesting the present invention.

國外寄存資訊[請依寄存國家、機構、日期、號碼順序註記] (1)嗜酸乳桿菌(Lactobacillus acidophilus)SBT2062菌株 寄存國家:日本 機構: 獨立行政法人 製品評價技術基盤機構專利微生物寄存中心，日本國千葉縣木更津市上總鎌足2-5-8 122號室(郵遞區號 292-0818) 日期: 1989年5月18日 號碼: FERM BP-11075 (2)瑞士乳桿菌(Lactobacillus helveticus)SBT2161菌株 寄存國家:日本 機構: 獨立行政法人 製品評價技術基盤機構專利微生物寄存中心，日本國千葉縣木更津市上總鎌足2-5-8 122號室(郵遞區號 292-0818) 日期: 2013年9月18日 號碼: NITE BP-1707 (3)瑞士乳桿菌(Lactobacillus helveticus)SBT2171菌株 寄存國家:日本 機構: 獨立行政法人 製品評價技術基盤機構專利微生物寄存中心，日本國千葉縣木更津市上總鎌足2-5-8 122號室(郵遞區號 292-0818) 日期: 1994年6月22日(原寄存日)、1996年3月6日(依原寄存基於布達佩斯條約移送至寄存的日期) 號碼: FERM BP-5445 (4)唾液乳桿菌(Lactobacillus salivarius)SBT2687菌株 寄存國家:日本 機構: 獨立行政法人 製品評價技術基盤機構專利微生物寄存中心，日本國千葉縣木更津市上總鎌足2-5-8 122號室(郵遞區號 292-0818) 日期: 2020年12月1日、2021年12月22日(依原寄存基於布達佩斯條約移送至寄存的日期) 號碼: NITE ABP-03331 (5)唾液乳桿菌(Lactobacillus salivarius)SBT2651菌株 寄存國家:日本 機構: 獨立行政法人 製品評價技術基盤機構專利微生物寄存中心，日本國千葉縣木更津市上總鎌足2-5-8 122號室(郵遞區號 292-0818) 日期: 2020年12月1日 號碼: NITE P-03330 (6)唾液乳桿菌唾液亞種(Lactobacillus salivarius subsp. salivarius)SBT2670菌株 寄存國家:日本 機構: 獨立行政法人 製品評價技術基盤機構專利微生物寄存中心，日本國千葉縣木更津市上總鎌足2-5-8 122號室(郵遞區號 292-0818) 日期: 1992年11月6日 號碼: FERM P-13247 (7)口腔鏈球菌(Streptococcus oralis)SBT0320菌株 寄存國家:日本 機構: 獨立行政法人 製品評價技術基盤機構專利微生物寄存中心，日本國千葉縣木更津市上總鎌足2-5-8 122號室(郵遞區號 292-0818) 日期: 2020年12月1日 號碼: NITE P-03332 (8)乳酸乳球菌乳酸亞種(Lactococcus lactis subsp. lactis)SBT0625菌株 寄存國家:日本 機構: 獨立行政法人 製品評價技術基盤機構專利微生物寄存中心，日本國千葉縣木更津市上總鎌足2-5-8 122號室(郵遞區號 292-0818) 日期: 2019年11月25日 號碼: NITE P-03078 (9)乳酸乳球菌乳脂亞種(Lactococcus lactis subsp. cremoris)SBT11373菌株 寄存國家:日本 機構: 獨立行政法人 製品評價技術基盤機構專利微生物寄存中心，日本國千葉縣木更津市上總鎌足2-5-8 122號室(郵遞區號 292-0818) 日期: 2020年7月14日 號碼: NITE P-03246 (10)勞氏乳球菌(Lactococcus laudensis)SBT11178菌株 寄存國家:日本 機構: 獨立行政法人 製品評價技術基盤機構專利微生物寄存中心，日本國千葉縣木更津市上總鎌足2-5-8 122號室(郵遞區號 292-0818) 日期: 2020年12月1日 號碼: NITE P-03333 (11)長雙歧桿菌(Bifidobacterium longum)SBT2928菌株 寄存國家:日本 機構: 獨立行政法人 製品評價技術基盤機構專利微生物寄存中心，日本國千葉縣木更津市上總鎌足2-5-8 122號室(郵遞區號 292-0818) 日期: 1989年4月13日 號碼: FERM P-10657 (12)長雙歧桿菌嬰兒亞種(Bifidobacterium longum subsp. infantis)SBT 2785菌株 寄存國家:日本 機構: 獨立行政法人 製品評價技術基盤機構專利微生物寄存中心，日本國千葉縣木更津市上總鎌足2-5-8 122號室(郵遞區號 292-0818) 日期: 2020年12月1日 號碼: NITE P-03328 (13)假長雙歧桿菌(Bifidobacterium pseudolongum)SBT2922菌株 寄存國家:日本 機構: 獨立行政法人 製品評價技術基盤機構專利微生物寄存中心，日本國千葉縣木更津市上總鎌足2-5-8 122號室(郵遞區號 292-0818) 日期: 2019年6月26日 號碼: NITE P-02984 (14)嗜熱雙歧桿菌(Bifidobacterium thermophilum)SBT2992菌株 寄存國家:日本 機構: 獨立行政法人 製品評價技術基盤機構專利微生物寄存中心，日本國千葉縣木更津市上總鎌足2-5-8 122號室(郵遞區號 292-0818) 日期: 2021年1月19日 號碼: NITE P-03364 Overseas storage information [please note in order of storage country, organization, date, number] (1) Lactobacillus acidophilus (Lactobacillus acidophilus) SBT2062 strain Storage country: Japan Institution: Independent Administrative Legal Person Product Evaluation Technology Base Organization Patent Microorganism Deposit Center, Room 122, 2-5-8, Kamiso Kamazu, Kisarazu City, Chiba Prefecture, Japan (Zip code 292-0818) Date: May 18, 1989 Number: FERM BP-11075 (2) Lactobacillus helveticus SBT2161 strain Storage country: Japan Institution: Independent Administrative Legal Person Product Evaluation Technology Base Organization Patent Microorganism Deposit Center, Room 122, 2-5-8, Kamiso Kamazu, Kisarazu City, Chiba Prefecture, Japan (Zip code 292-0818) Date: September 18, 2013 Number: NITE BP-1707 (3) Lactobacillus helveticus SBT2171 strain Storage country: Japan Institution: Independent Administrative Legal Person Product Evaluation Technology Base Organization Patent Microorganism Deposit Center, Room 122, 2-5-8, Kamiso Kamazu, Kisarazu City, Chiba Prefecture, Japan (Zip code 292-0818) Date: June 22, 1994 (the date of the original deposit), March 6, 1996 (the date when the original deposit was transferred to the deposit based on the Budapest Treaty) Number: FERM BP-5445 (4) Lactobacillus salivarius (Lactobacillus salivarius) SBT2687 strain Storage country: Japan Institution: Independent Administrative Legal Person Product Evaluation Technology Base Organization Patent Microorganism Deposit Center, Room 122, 2-5-8, Kamiso Kamazu, Kisarazu City, Chiba Prefecture, Japan (Zip code 292-0818) Date: December 1, 2020, December 22, 2021 (the date when the original deposit was transferred to the deposit based on the Budapest Treaty) Number: NITE ABP-03331 (5) Lactobacillus salivarius SBT2651 strain Storage country: Japan Institution: Independent Administrative Legal Person Product Evaluation Technology Base Organization Patent Microorganism Deposit Center, Room 122, 2-5-8, Kamiso Kamazu, Kisarazu City, Chiba Prefecture, Japan (Zip code 292-0818) Date: December 1, 2020 Number: NITE P-03330 (6) Lactobacillus salivarius subsp. salivarius SBT2670 strain Storage country: Japan Institution: Independent Administrative Legal Person Product Evaluation Technology Base Organization Patent Microorganism Deposit Center, Room 122, 2-5-8, Kamiso Kamazu, Kisarazu City, Chiba Prefecture, Japan (Zip code 292-0818) Date: November 6, 1992 Number: FERM P-13247 (7) Streptococcus oralis SBT0320 strain Storage country: Japan Institution: Independent Administrative Legal Person Product Evaluation Technology Base Organization Patent Microorganism Deposit Center, Room 122, 2-5-8, Kamiso Kamazu, Kisarazu City, Chiba Prefecture, Japan (Zip code 292-0818) Date: December 1, 2020 Number: NITE P-03332 (8) Lactococcus lactis subsp. lactis SBT0625 strain Storage country: Japan Institution: Independent Administrative Legal Person Product Evaluation Technology Base Organization Patent Microorganism Deposit Center, Room 122, 2-5-8, Kamiso Kamazu, Kisarazu City, Chiba Prefecture, Japan (Zip code 292-0818) Date: November 25, 2019 Number: NITE P-03078 (9) Lactococcus lactis subsp. cremoris SBT11373 strain Storage country: Japan Institution: Independent Administrative Legal Person Product Evaluation Technology Base Organization Patent Microorganism Deposit Center, Room 122, 2-5-8, Kamiso Kamazu, Kisarazu City, Chiba Prefecture, Japan (Zip code 292-0818) Date: July 14, 2020 Number: NITE P-03246 (10) Lactococcus laudensis SBT11178 strain Storage country: Japan Institution: Independent Administrative Legal Person Product Evaluation Technology Base Organization Patent Microorganism Deposit Center, Room 122, 2-5-8, Kamiso Kamazu, Kisarazu City, Chiba Prefecture, Japan (Zip code 292-0818) Date: December 1, 2020 Number: NITE P-03333 (11) Bifidobacterium longum (Bifidobacterium longum) SBT2928 strain Storage country: Japan Institution: Independent Administrative Legal Person Product Evaluation Technology Base Organization Patent Microorganism Deposit Center, Room 122, 2-5-8, Kamiso Kamazu, Kisarazu City, Chiba Prefecture, Japan (Zip code 292-0818) Date: April 13, 1989 Number: FERM P-10657 (12) Bifidobacterium longum subsp. infantis SBT 2785 strain Storage country: Japan Institution: Independent Administrative Legal Person Product Evaluation Technology Base Organization Patent Microorganism Deposit Center, Room 122, 2-5-8, Kamiso Kamazu, Kisarazu City, Chiba Prefecture, Japan (Zip code 292-0818) Date: December 1, 2020 Number: NITE P-03328 (13) Bifidobacterium pseudolongum SBT2922 strain Storage country: Japan Institution: Independent Administrative Legal Person Product Evaluation Technology Base Organization Patent Microorganism Deposit Center, Room 122, 2-5-8, Kamiso Kamazu, Kisarazu City, Chiba Prefecture, Japan (Zip code 292-0818) Date: June 26, 2019 Number: NITE P-02984 (14) Bifidobacterium thermophilum SBT2992 strain Storage country: Japan Institution: Independent Administrative Legal Person Product Evaluation Technology Base Organization Patent Microorganism Deposit Center, Room 122, 2-5-8, Kamiso Kamazu, Kisarazu City, Chiba Prefecture, Japan (Zip code 292-0818) Date: January 19, 2021 Number: NITE P-03364

Figure 12_A0101_SEQ_0001
Figure 12_A0101_SEQ_0001

Figure 12_A0101_SEQ_0002
Figure 12_A0101_SEQ_0002

Figure 12_A0101_SEQ_0003
Figure 12_A0101_SEQ_0003

Figure 12_A0101_SEQ_0004
Figure 12_A0101_SEQ_0004

Figure 12_A0101_SEQ_0005
Figure 12_A0101_SEQ_0005

Figure 12_A0101_SEQ_0006
Figure 12_A0101_SEQ_0006

Claims (15)

一種關節功能改善用組成物，含有屬於乳桿菌(Lactobacillus)屬、乳球菌(Lactococcus)屬、鏈球菌(Streptococcus)屬、或雙歧桿菌(Bifidobacterium)屬的菌的菌體及/或其培養物作為有效成分。A composition for improving joint function, comprising bacterial cells and/or cultures thereof belonging to the genus Lactobacillus, Lactococcus, Streptococcus, or Bifidobacterium as an active ingredient. 如請求項1之關節功能改善用組成物，其中，屬於乳桿菌屬、乳球菌屬、鏈球菌屬、或雙歧桿菌屬的菌，係選自嗜酸乳桿菌(Lactobacillus acidophilus)、瑞士乳桿菌(Lactobacillus helveticus)、唾液乳桿菌(Lactobacillus salivarius)、乳酸乳球菌(Lactococcus lactis)、勞氏乳球菌(Lactococcus laudensis)、口腔鏈球菌(Streptococcus oralis)、長雙歧桿菌(Bifidobacterium longum)、假長雙歧桿菌(Bifidobacterium pseudolongum)、嗜熱雙歧桿菌(Bifidobacterium thermophilum)中之一種以上。The composition for improving joint function as claimed in claim 1, wherein the bacteria belonging to the genus Lactobacillus, Lactococcus, Streptococcus, or Bifidobacterium are selected from Lactobacillus acidophilus, Lactobacillus helveticus (Lactobacillus helveticus), Lactobacillus salivarius, Lactococcus lactis, Lactococcus laudensis, Streptococcus oralis, Bifidobacterium longum, Bifidobacterium longum One or more of Bifidobacterium pseudolongum and Bifidobacterium thermophilum. 如請求項2之關節功能改善用組成物，其中，屬於唾液乳桿菌、乳酸乳球菌、或長雙歧桿菌的菌，係屬於唾液乳桿菌唾液亞種(Lactobacillus salivarius subsp. salivarius)、乳酸乳球菌乳酸亞種(Lactococcus lactis subsp. lactis)、乳酸乳球菌乳脂亞種(Lactococcus lactis subsp. cremoris)、或長雙歧桿菌嬰兒亞種(Bifidobacterium longum subsp. infantis)的菌。Such as the joint function improvement composition of claim 2, wherein the bacteria belonging to Lactobacillus salivarius, Lactococcus lactis, or Bifidobacterium longum belong to Lactobacillus salivarius subsp. salivarius, Lactococcus lactis Lactococcus lactis subsp. lactis, Lactococcus lactis subsp. cremoris, or Bifidobacterium longum subsp. infantis. 如請求項1至3中任一項之關節功能改善用組成物，其中，屬於乳桿菌屬、乳球菌屬、鏈球菌屬、或雙歧桿菌屬的菌，係選自嗜酸乳桿菌(Lactobacillus acidophilus)SBT2062菌株(FERM BP-11075)、瑞士乳桿菌(Lactobacillus helveticus)SBT2161菌株(NITE BP-1707)、SBT2171菌株(FERM BP-5445)、唾液乳桿菌(Lactobacillus salivarius)SBT2687菌株(NITE ABP-03331)、SBT2651菌株(NITE P-03330)、唾液乳桿菌唾液亞種(Lactobacillus salivarius subsp. salivarius)SBT2670菌株(FERM P-13247)、乳酸乳球菌乳酸亞種(Lactococcus lactis subsp. lactis)SBT0625菌株(NITE P-03078)、乳酸乳球菌乳脂亞種(Lactococcus lactis subsp. cremoris)SBT11373菌株(NITE P-03246)、勞氏乳球菌(Lactococcus laudensis)SBT11178菌株(NITE P-03333)、口腔鏈球菌(Streptococcus oralis)SBT0320菌株(NITE P-03332)、長雙歧桿菌(Bifidobacterium longum)SBT2928菌株(FERM P-10657)、長雙歧桿菌嬰兒亞種(Bifidobacterium longum subsp. infantis)SBT2785菌株(NITE P-03328)、假長雙歧桿菌(Bifidobacterium pseudolongum)SBT2922菌株(NITE P-02984)、嗜熱雙歧桿菌(Bifidobacterium thermophilum)SBT2992菌株(NITE P-03329)中之一種以上。The composition for improving joint function according to any one of claims 1 to 3, wherein the bacteria belonging to the genus Lactobacillus, Lactococcus, Streptococcus, or Bifidobacterium are selected from the group consisting of Lactobacillus acidophilus) SBT2062 strain (FERM BP-11075), Lactobacillus helveticus SBT2161 strain (NITE BP-1707), SBT2171 strain (FERM BP-5445), Lactobacillus salivarius (Lactobacillus salivarius) SBT2687 strain (NITE ABP-03331 ), SBT2651 strain (NITE P-03330), Lactobacillus salivarius subsp. salivarius SBT2670 strain (FERM P-13247), Lactococcus lactis subsp. lactis SBT0625 strain (NITE P-03078), Lactococcus lactis subsp. cremoris SBT11373 strain (NITE P-03246), Lactococcus laudensis SBT11178 strain (NITE P-03333), Streptococcus oralis ) SBT0320 strain (NITE P-03332), Bifidobacterium longum SBT2928 strain (FERM P-10657), Bifidobacterium longum subsp. infantis SBT2785 strain (NITE P-03328), One or more of Bifidobacterium pseudolongum SBT2922 strain (NITE P-02984) and Bifidobacterium thermophilum SBT2992 strain (NITE P-03329). 一種關節功能改善劑、關節功能改善用飲食品、關節功能改善用營養組成物、關節功能改善用飼料或關節功能改善用醫藥品，其特徵在於，含有如請求項1至4中任一項之關節功能改善用組成物。A joint function improving agent, a food and drink for joint function improvement, a nutritional composition for joint function improvement, a feed for joint function improvement, or a drug for joint function improvement, characterized in that it contains any one of claims 1 to 4 A composition for improving joint function. 一種新穎之乳酸菌，係唾液乳桿菌(Lactobacillus salivarius)SBT2687菌株。A novel lactic acid bacterium is Lactobacillus salivarius (Lactobacillus salivarius) SBT2687 strain. 一種新穎之乳酸菌，係唾液乳桿菌(Lactobacillus salivarius)SBT2651菌株。A novel lactic acid bacterium is Lactobacillus salivarius SBT2651 strain. 一種勞氏乳球菌(Lactococcus laudensis)，係SBT11178菌株。A kind of Lactococcus laudensis (Lactococcus laudensis), is strain SBT11178. 一種新穎之乳酸菌，係口腔鏈球菌(Streptococcus oralis)SBT0320菌株。A novel lactic acid bacterium is Streptococcus oralis SBT0320 strain. 一種新穎之雙歧桿菌，係長雙歧桿菌嬰兒亞種(Bifidobacterium longum subsp. infantis)SBT2785菌株。A novel bifidobacterium, which is Bifidobacterium longum subsp. infantis SBT2785 strain. 一種新穎之雙歧桿菌，係嗜熱雙歧桿菌(Bifidobacterium thermophilum)SBT2992菌株。A novel bifidobacterium is a strain of Bifidobacterium thermophilum SBT2992. 一種屬於乳桿菌(Lactobacillus)屬、乳球菌(Lactococcus)屬、鏈球菌(Streptococcus)屬、或雙歧桿菌(Bifidobacterium)屬的菌的菌體及/或其培養物的用途，係用來製造關節功能改善用組成物。A use of bacteria and/or cultures thereof belonging to the genus Lactobacillus, Lactococcus, Streptococcus, or Bifidobacterium for the manufacture of joints Composition for function improvement. 一種屬於乳桿菌(Lactobacillus)屬、乳球菌(Lactococcus)屬、鏈球菌(Streptococcus)屬、或雙歧桿菌(Bifidobacterium)屬的菌的菌體及/或其培養物，係用來改善關節功能。A bacterial cell and/or culture thereof belonging to the genus Lactobacillus, Lactococcus, Streptococcus, or Bifidobacterium is used to improve joint function. 一種關節功能改善方法，包含下述步驟： 將有效量之屬於乳桿菌(Lactobacillus)屬、乳球菌(Lactococcus)屬、鏈球菌(Streptococcus)屬、或雙歧桿菌(Bifidobacterium)屬的菌的菌體及/或其培養物，給需要的對象攝取、或投予給需要的對象。 A method for improving joint function, comprising the steps of: An effective amount of bacterial cells and/or cultures thereof belonging to the genus Lactobacillus, Lactococcus, Streptococcus, or Bifidobacterium is administered to the subject in need Ingest or administer to a subject in need. 一種促進軟骨細胞增殖用、抑制發炎因子產生用、抑制軟骨基質分解因子產生用、抑制疼痛因子產生用、及/或抑制神經伸長因子產生用組成物，含有屬於乳桿菌(Lactobacillus)屬、乳球菌(Lactococcus)屬、鏈球菌(Streptococcus)屬、或雙歧桿菌(Bifidobacterium)屬之菌的菌體及/或其培養物作為有效成分。A composition for promoting the proliferation of chondrocytes, inhibiting the production of inflammatory factors, inhibiting the production of cartilage matrix decomposition factors, inhibiting the production of pain factors, and/or inhibiting the production of nerve elongation factors, comprising Lactobacillus, Lactococcus (Lactococcus) genus, Streptococcus (Streptococcus) genus, or Bifidobacterium (Bifidobacterium) genus bacteria and/or cultures thereof are used as active ingredients.
TW111101373A 2021-01-26 2022-01-13 Composition for improving joint function TW202239958A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2021010460 2021-01-26
JP2021-010460 2021-01-26

Publications (1)

Publication Number Publication Date
TW202239958A true TW202239958A (en) 2022-10-16

Family

ID=82653356

Family Applications (1)

Application Number Title Priority Date Filing Date
TW111101373A TW202239958A (en) 2021-01-26 2022-01-13 Composition for improving joint function

Country Status (9)

Country Link
US (1) US20240075081A1 (en)
EP (1) EP4285997A1 (en)
JP (1) JPWO2022163323A1 (en)
KR (1) KR20230138497A (en)
CN (1) CN117460427A (en)
AU (1) AU2022213579A1 (en)
CA (1) CA3208281A1 (en)
TW (1) TW202239958A (en)
WO (1) WO2022163323A1 (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116195742B (en) * 2021-11-30 2024-07-09 内蒙古伊利实业集团股份有限公司 Application of bifidobacterium lactis BL-99 in cartilage protection

Family Cites Families (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH1084909A (en) * 1996-09-13 1998-04-07 Snow Brand Milk Prod Co Ltd Intestinal butyric acid concentration increase accelerating agent
AU2002249531A1 (en) * 2001-04-02 2002-10-28 Alimentary Health Limited Immunotherapy based on dendritic cells
JP4377117B2 (en) * 2002-09-03 2009-12-02 株式会社エイ・エル・エイ Composition for improving inflammatory diseases
WO2004087178A1 (en) * 2003-03-31 2004-10-14 Alimentary Health Limited A formulation comprising a bacterial strain
GB0323039D0 (en) * 2003-10-01 2003-11-05 Danisco Method
HUP0700552A2 (en) * 2007-08-27 2009-03-30 Janos Dr Feher Method and composition inhibiting inflammation
NL1034964C2 (en) * 2008-01-28 2009-07-30 Friesland Brands Bv Method and compositions for the treatment of bone disorders.
JP5840368B2 (en) * 2011-02-02 2016-01-06 カルピス株式会社 Substances for preventing and improving arthritis
KR101355440B1 (en) * 2011-10-26 2014-02-05 주식회사한국야쿠르트 Lactobacillus helveticus HY7801 having anti- rheumatoid arthritis functions, and products containing thereof as effective component
JP6491422B2 (en) * 2013-09-26 2019-03-27 雪印メグミルク株式会社 Immune disease preventive
CN104546944B (en) * 2014-09-30 2019-02-01 深圳华大基因科技有限公司 Lactococcus lactis is treating or preventing the application in rheumatoid arthritis or its related disease
JP2015096555A (en) * 2015-02-10 2015-05-21 雪印メグミルク株式会社 Preventive, improving, and therapeutic agent for metabolic disorder with aging
KR102069807B1 (en) * 2017-03-09 2020-01-28 가톨릭대학교 산학협력단 Composition for preventing or treating immune diseases comprising mixture of lactic acid bacteria
KR102050265B1 (en) * 2017-03-13 2019-12-02 가톨릭대학교 산학협력단 Composition for treating or preventing of arthritis, fibrosis, colitis or transplant rejection comprising Lactobacillus Acidophilus
CA3056715A1 (en) * 2017-03-15 2018-09-20 University Of Rochester Compositions of oligofructose and commensal microorganisms and methods thereof
JP6799673B2 (en) * 2017-03-30 2020-12-16 森永乳業株式会社 Composition for promoting expression of inflammation control gene
AU2018367596A1 (en) * 2017-11-15 2020-05-21 Evelo Biosciences, Inc. Compositions and methods for treating immune disorders using immune modulating
CN112074193A (en) * 2018-01-29 2020-12-11 精密生物集团有限公司 A composition for preventing and treating irritable bowel syndrome
KR102185981B1 (en) * 2018-02-28 2020-12-03 주식회사 엠디헬스케어 Nanovesicles derived from Streptococcus bacteria and Use thereof
WO2019178309A1 (en) * 2018-03-14 2019-09-19 Sustainable Community Development, Llc Probiotic composition and feed additive
KR102074445B1 (en) * 2018-12-12 2020-02-06 주식회사 비피도 Bifidobacterium longum RAPO for improvement, prevention or treatment of rheumatoid arthritis and composition comprising the same
JP7220457B2 (en) 2018-12-14 2023-02-10 丸善製薬株式会社 Hyaluronic acid production promoter, joint function improving agent, and oral composition
KR20200131658A (en) * 2019-05-14 2020-11-24 한국식품연구원 Composition for preventing, improving, or treating of arthromyalgia, headache, or colpoxerosis of menopausal female comprising Lactobacillus acidophilus
JPWO2021112041A1 (en) * 2019-12-02 2021-06-10
CN112155207A (en) * 2020-04-15 2021-01-01 杭州劲膳美健康管理有限公司 Medical formula food for rheumatoid arthritis and preparation method thereof
CN112023030A (en) * 2020-09-09 2020-12-04 山东润德生物科技有限公司 Ammonia sugar probiotic bone collagen peptide formula for nursing bone joint neogenesis

Also Published As

Publication number Publication date
WO2022163323A1 (en) 2022-08-04
EP4285997A1 (en) 2023-12-06
US20240075081A1 (en) 2024-03-07
KR20230138497A (en) 2023-10-05
AU2022213579A9 (en) 2024-05-02
AU2022213579A1 (en) 2023-08-10
CA3208281A1 (en) 2022-08-04
JPWO2022163323A1 (en) 2022-08-04
CN117460427A (en) 2024-01-26

Similar Documents

Publication Publication Date Title
JP7273725B2 (en) Novel bifidobacterium bacterium and composition containing the bacterium
EP2305838B1 (en) Bifidobacteria that produces folic acid, food composition and use of said bifidobacteria
DK2478910T3 (en) ANTI-ADIPOSITY AGENT, ANTI-ADIPOSITA NUTRITION OR DRINK, GLUCOSE TOLERANCE EFFECTIVE AGENT, AND NUTRITION OR DRINK FOR IMPROVING GLUCOSE TOLERANCE
TWI594758B (en) Composition comprising bifidobacteria,processes for the preparation thereof and uses thereof
CN109069555B (en) Composition for improving brain function for newborn
AU2007292786B2 (en) Agent for accelerating the increase in and/or preventing the decrease in blood adiponectin level, and visceral fat accumulation inhibitor
CN106604736A (en) Use of lactobacillus paracasei for promoting recovery of the intestinal microbiota diversity after dysbiosis
WO2021112041A1 (en) Bone-strengthening agent
JP7240327B2 (en) Novel bifidobacterium bacterium and composition containing the bacterium
AU2019241546A1 (en) Sleep-promoting composition, and medicinal composition and food and beverage composition using said sleep-promoting composition
KR102224072B1 (en) Bifidobacterium longum subsp. longum having both abilities of reducing total cholesterol in serum and immune regulation and its application
TW202239958A (en) Composition for improving joint function
JP6761268B2 (en) MKP-1 inducer
BR122022016606B1 (en) LACTOBACILLUS PARACASEI DEAD BY HEATING, DRUG, FOOD OR DRINK, FEED, AGENT PROMOTING IL-12 PRODUCTION AND USE
CN115838675A (en) Lactobacillus rhamnosus and composition and application thereof
JP2004315477A (en) Bone resorption inhibitor
JPWO2018003898A1 (en) Composition for promoting cartilage regeneration
TW202207957A (en) Novel bifidobacterium breve idcc 4401 strain having high resistance ability of acid and bile salt and effect of preventing or treating dyslipidemia, and their killed form id-bbr4401
EP2437758A1 (en) Bacteria thya(-) mutants with increased vitamin k
TW201717783A (en) Materials and methods for improving gastrointestinal health
CN110839693A (en) Application of parabacteroides gibsonii in preventing or treating obesity or related diseases
JP6487106B1 (en) Food composition for improving immune function
RU2729633C2 (en) Biologically active food additive for preventing inflammatory intestinal disease and functional intestinal disorders and a method for production thereof
JP2003238423A (en) Hypocholesterolemic agent and hypocholesterolemic food and beverage
JP2003252771A (en) Agent for prevention, improvement and treatment of age-related metabolic disorder